The Biomedical & Life Sciences Collection
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The Biomedical & Life Sciences Collection

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305 Pages
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25 Feb 2010 – Prior to coming to UCLA, he did postdoctoral work at the Whitehead. Institute for ...... Jim Putney completed a PhD at the Medical College of Virginia and postdoctoral training at the ...... King's College London (http://www.microsatellites.org). Heritability ...... a post-doc with R. L. Baldwin at Stanford University.

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The Biomedical & Life Sciences CollectionListing of the Online Seminar Style Talks Available to date
Beth February 15,2010
This document contains all of the talks currently available for viewing on The Biomedical & Life Sciences Collection. It should be noted that the collection is edited and updated on a monthly basis. The amount of talks available, specially commissioned by many of the world’s leading scientists is increased by approximately 10-15 talks per month.
The Biomedical & Life Sciences Collection Online Seminar Style Talks Available at 15th February 2010
Talk and Speaker Biography
Transcriptional ActivationProf. Arnold Berk - University of California, Los Angeles, USAArnold Berk received his MD degree from Stanford University School of Medicine where he participated in the Medical Scientist Training Program. After post-doctoral training with Philip A. Sharp at MIT, where he participated in the discovery of RNA splicing, he moved to a faculty position at the University of California, Los Angeles in the Molecular Biology Institute and the Department of Microbiology, Immunology and Molecular Genetics. Dr. Berk's current research focuses on the regulation of transcription initiation by the adenovirus E1A protein and other aspects of adenovirus molecular biology.
The Regulation of Pre-Messenger RNA SplicingProf. Douglas Black - University of California, Los Angeles, USADouglas Black is a Professor in the Department of Microbiology, Immunology and Molecular Genetics at UCLA, and an Investigator of the Howard Hughes Medical Institute. He received his Bachelor's degree in Chemistry from UC Santa Cruz in 1982, and his PhD in Molecular Biophysics and Biochemistry from Yale in 1987. Prior to coming to UCLA, he did postdoctoral work at the Whitehead Institute for Biomedical Research at MIT.
Dynamic chromatin: ATP-dependent chromatin remodeling machinesProf. Bradley Cairns - University of Utah School of Medicine, USABrad Cairns is an Associate Professor of Oncological Sciences in the Hunstman Cancer Institute at the University of Utah School of Medicine. He is also an Investigator with the Howard Hughes Medical Institute. Prof. Cairns received his Bachelor of Science degree in Chemistry from Lewis and Clark College in 1987, and then spent a year working in molecular parasitology with Scott Landfear at the Oregon Health Sciences University. In 1995, he received his PhD in Cell Biology from Stanford University, where he worked with Roger Kornberg on MAP kinase signaling and chromatin remodeling complexes. Prof. Cairns then worked with Fred Winston in the Department of Genetics at Harvard Medical School, where he pursued genetic and molecular analyses of chromatin remodeling. He joined the faculty at Utah in 1998, and HHMI in 2000. His laboratory utilizes biochemical, molecular, genetic and genomic approaches to understand how chromatin helps regulate gene expression.
Topics discussed
Transcription by RNA polymerase II | Mediator complex | Coactivator proteins | Communication between DNA-binding proteins and general transcription machinery
Molecular mechanisms of the basic splicing reaction | Spliceosome assembly | Exon definition | Splicing enhancer and silencer elements | RNA binding proteins that regulate splicing | Protein diversity in metazoan organisms | Tissue specific splicing | Drosophila sex determination pathway | Complex regulation of alternative splicing in mammals
ATP-dependent chromatin remodeling complexes | ATP hydrolysis and nucleosome dynamics | Mechanistic action | Cellular function
The Beta-Globin LocusDr. Ann Dean - National Institutes of Health, USAAnn Dean is a Senior Investigator in the Laboratory of Cellular and Developmental Biology, NIDDK, NIH. She received her PhD from George Washington University and did postdoctoral studies at the NIH in the laboratory of Dr. Robert T. Simpson. Her main interests are in the role of chromatin structure in gene transcription and, in particular, regulation of the human beta-globin genes. She combines basic research looking at the epigenetic state of the chromatin milieu in which the globin genes reside with studies of the role of erythroid transcription factors in the developmental progression of the expression of these genes, an area of investigation relevant to therapeutic interventions in sickle cell disease and beta-thalassemia.
The E2F Family and Transcriptional Control of the Mammalian Cell Cycle Prof. Brian Dynlacht - New York University School of Medicine and NYU Cancer Institute, USABrian Dynlacht graduated from Yale University in 1987 with a BS in Molecular Biophysics and Biochemistry, after which he performed his graduate studies at the University of California, Berkeley. After his postdoctoral studies at Harvard Medical School (Massachusetts General Hospital), he assumed an assistant professor position at Harvard University. He left Harvard University in 2002 and became Associate Professor of Pathology at the New York University School of Medicine and Director of the NYU Cancer Institute Genomics Program.
Genome-Wide Analyses of Protein-DNA InteractionsProf. Peggy Farnham - University of California in Davis, USAPeggy Farnham obtained her PhD from Yale University in 1982, which is when she began working on transcriptional regulation. This topic was also the focus on Dr. Farnham's postdoctoral work at Stanford University (1982-1986) and became the cornerstone of her lab research when she joined the faculty at the McArdle Laboratory for Cancer Research at the University of Wisconsin in Madison in 1987. While at the University of Wisconsin, she also served as Chair of the Cellular and Molecular Biology PhD Degree Program from 1996-2002. Major scientific contributions that came from Dr. Farnham's research at the University of Wisconsin include the identification of the E2F and Myc families of transcription factors as key mediators of the G1/S-phase transition of the mammalian cell cycle and the development of in-vivo DNA-protein assays to study transcription factor binding to promoter regions using living cells. Over the last two decades, the questions addressed in her lab have evolved from a detailed analysis of the transcriptional regulation of particular genes to a desire to investigate transcriptional regulation using a more global approach. Therefore, in August 2004, Dr. Farnham relocated her laboratory to the Genome Center at the University of California in Davis. She is now a Professor of Pharmacology and the Associate Director of Genomics at the Genome Center of UC Davis. Her current studies are focused on the development of high throughput, global analyses of transcription factors using methods that combine chromatin immunoprecipitation with genomic microarray hybridization. Dr. Farnham's laboratory is very involved with the Encyclopedia of DNA Elements (ENCODE) project organized by the National Human Genome Research Institute (NHGRI). The goal of this large project is to bring together diverse investigators to develop methods that can be applied towards the identification of all the functional elements in the human genome (see Science 306: 636-640, 2004).
Transcription of beta-globin family of genes | Regulation of gene expression during human development | Locus control region (LCR) | DNase I hypersensitive sites in chromatin | Transcription factors including GATA-1, EKLF and NF-E2 | Implications for sickle cell disease and beta-thalassemia | Latest findings and future challenges
Complex and diverse roles of E2F family members | Interaction with tumour repressor proteins | Interaction with chromatin modifying enzymes | Study using microarray technology and chromatin immunoprecipitation | Novel features of cell cycle dependent transcription | Roles in regulating G1-to-S transition, mitosis, differentiation, and apoptosis
Identifying genomic targets of DNA-binding factors | Experimental methods | Chromatin immunoprecipitation (ChIP) assay | Probing microarrays | ChIP-on-chip assays for comprehensive analysis | Data interpretation and follow-up studies
The Transcription Factor NF-Kappa B: an Evolutionarily Conserved Mediator of Immune and Inflammatory ResponsesProf. Sankar Ghosh - Yale University School of Medicine, USASankar Ghosh received his PhD in Biochemistry and Biophysics from the Albert Einstein College of Medicine, New York, in 1988. After postdoctoral training with David Baltimore at the Whitehead Institute, MIT, in 1991 he moved to a faculty position at Yale University School of Medicine in the Section of Immunobiology and Department of Molecular Biophysics and Biochemistry. Dr. Ghosh's research program is focused on understanding how engagement of receptors of both the innate and adaptive immune system lead to the activation of appropriate cellular responses through the inducible transcription factor, NF-kappa B.
The RNA Polymerase II General Transcription MachineryProf. Michael Hampsey - University of Medicine and Dentistry of New Jersey, USAMichael Hampsey is a native of the Finger Lakes region of New York State. He earned his BS degree in chemistry at the State University of New York at Geneseo and PhD in biochemistry at Purdue University. Following postdoctoral training in yeast genetics at the University of Rochester he was on the faculty at Louisiana State University Medical School in Shreveport. He is currently Professor of Biochemistry at the University of Medicine and Dentistry of New Jersey and member of the UMDNJ - Master Educators' Guild. He lives with his wife Eileen and their three children in Metuchen, New Jersey.
Coupling Transcription, RNA Processing and RNA ExportProf. Grant Hartzog - University of California, Santa Cruz, USAGrant Hartzog received his PhD in Biochemistry and Biophysics from the University of California, San Francisco in 1992. After postdoctoral training with Fred Winston at Harvard Medical School, he moved to a faculty position at the University of California Santa Cruz in the Department of Molecular, Cell and Developmental Biology. Dr. Hartzog's research program focuses on studies of the regulation of transcription elongation and its connections to chromatin structure and RNA processing in yeast.
DNA MethylationProf. Steve Jacobsen - University of California, Los Angeles, USASteve Jacobsen is an HHMI Investigator and a Professor in the Department of Molecular, Cell and Developmental Biology. His research centers on genetic studies of DNA methylation control in the plant, Arabidopsis thaliana.
Visualization of Transcription Factor Interactions in Living CellsProf. Tom Kerppola - University of Michigan, USATom Kerppola is a Professor of Biological Chemistry and an Investigator of the Howard Hughes Medical Institute at the University of Michigan Medical School. Dr. Kerppola's laboratory investigates transcription factor interactions and the architecture of nucleoprotein complexes. Dr. Kerppola obtained his PhD with Dr. Michael Chamberlin and Dr. Caroline Kane at the University of California, Berkeley and was a Helen Hay Whitney Postdoctoral Fellow with Dr. Tom Curran.
NF-kappa B activation and function | Signal transduction pathway | Mechanism of post-transcriptional induction | Gene activation | Role of NF-kappa B in physiological processes | Initiation of the immune system | Cell survival
Core promoters | Enhancers and silencers | General transcription factors | RNAP II | Mechanism of initiation
Mechanistic coupling of RNA processing, export and transcription | Current evidence supporting coupling mechanisms | Role of the RNA polymerase II CTD | Competition during transcription between RNA binding proteins | Future challenges and directions
Roles of DNA methylation | Evolution of eukaryotic DNA methyltransferases | Mechanism of action of DNA methyltransferases | Specific loci targeting | Histone modification | Small interfering RNA
Transcription regulatory proteins | Combinatorial control of gene expression | Visualization of transcription factor interactions and modifications in living cells | New methods development | Bimolecular fluorescence complementation (BiFC) assays | Ubiquitin mediated fluorescence complementation (UbFC) assays
Epigenetic Information in Gene Expression and CancerProf. Siavash Kurdistani - University of California, Los Angeles, USASiavash Kurdistani received his BS in Biochemistry from UCLA (1994) and MD from Harvard Medical School (1999). He was awarded a Howard Hughes Medical Institute Postdoctoral Fellowship for Physicians in 2001. Currently he is an Assistant Professor in the Department of Biological Chemistry at the David Geffen School of Medicine, UCLA.
Introduction to Chromatin StructureProf. Karolin Luger - Colorado State University, USAKarolin Luger received her PhD in Biochemistry from the Biocenter (University of Basel), and then proceeded to do a postdoc with Dr. Tim Richmond at the Swiss Federal Institute in Zurich where the structure of the nucleosome core particle was determined first at 2.8, then at 1.9 Angstrom resolution. Dr. Luger started her own laboratory at Colorado State University in Fort Collins in 1999, and was promoted to Associate Professor in 2003. In 2005, she was named an HHMI investigator. Dr. Luger's lab focuses on elucidating the structure and dynamics of nucleosomes, and aims at understanding how the nucleosomes interface with the transcription machinery. To this end, the lab group are using X-ray crystallography, fluorescence techniques, analytical ultracentrifugation and standard techniques in molecular biology.
The Mechanisms and Control of mRNA Turnover in Eukaryotic CellsProf. Roy Parker - University of Arizona, USARoy Parker is Regents Professor of Molecular and Cellular Biology at the University of Arizona and Investigator for Howard Hughes Medical Institute. He also holds a joint appointment in the Department of Biochemistry and the Arizona Cancer Center. He received his PhD degree in genetics from the University of California, San Francisco, and was a postdoctoral fellow at the University of Massachusetts Medical School. Roy Parker is interested in the biogenesis, function and degradation of eukaryotic mRNA, and how cells regulate different steps in this process to modulate gene expression.
Histone Modification and Transcriptional RepressionDr. Yang Shi - Harvard Medical School, USAYang Shi received his PhD from New York University in 1988. After postdoctoral training with Thomas Shenk at Princeton, he moved to a faculty position at Harvard Medical School in the Department of Pathology. Dr. Shi's research program focuses on studies of regulation of transcription and chromatin modifications in development and cancer, using cell culture, mouse, C. elegans and S. pombe as models.
Types and functions of histone modifications | Histone code hypothesis | Epigenetics and transcription regulation | Relevance for human disease
Chromatin and differential regulation of transcription | Basic structure and properties of a nucleosome | Current knowledge on higher order chromatin structures
Control of mRNA degradation | Modulation in response to physiological cues | Mechanisms of mRNA turnover | Critical nucleases | Sequence-specific binding of regulators | Rates of turnover | mRNA decay and viral infections | Role in recognizing aberrant mRNAs
Mechanisms of transcriptional repression | Corepressor proteins | Histone modifications involved in repression | Cancer
Transcription Elongation Control by RNA Polymerase IIProf. Ali Shilatifard - Saint Louis University School of Medicine , USAAli Shilatifard, Professor of Biochemistry and Associate Scientific Director at Saint Louis University Cancer Center, is primarily interested in defining the molecular mechanism for the pathogenesis of Acute Myeloid Leukemia (AML) in children caused by chromosomal translocations involving the MLL gene. His laboratory has identified the role for one of the MLL translocation partners, the ELL protein, as an RNA polymerase II elongation factor. He has also demonstrated that the MLL homologue in yeast, the Set1 protein, exists in a large macromolecular complex he calls COMPASS. COMPASS functions as a histone H3 lysine 4 methyltransferase. Recently it has been demonstrated that MLL is also a methyltransferase similar to COMPASS. Dr. Shilatifard's current interests focus on three areas: 1) defining the molecular mechanism of histone methylation by COMPASS and MLL complexes; 2) understanding why MLL translocations result in the pathogenesis of leukemia; and 3) identify inhibitors of COMPASS and MLL functions in the hope of developing targeted therapies for the treatment of AML associated with MLL translocations. In recognition of his scientific discoveries, Dr. Shilatifard has been appointed as a Scholar of the Leukemia and Lymphoma Society and was awarded the Sword of the American Cancer Society by the Heartland Chapter. He has also received the ASBMB-Amgen Award which is given annually by the American Society for Biochemistry and Molecular Biology to a scientist whose biochemical research has made major contributions to understanding diseases. He has also been serving on the Editorial Boards of the ''Journal of Biological Chemistry'', and has been a member on the study sections both for National Institutes of Health and the American Cancer Society. Dr. Shilatifard is also committed to teaching at multiple levels. He is involved with both graduate and medical school teaching at Saint Louis University Medical Center, and also serves as an instructor for the Gene Expression course at the Cold Spring Harbor Laboratory. He is married to Laura Shilatifard, and has four children, Francesca, Natalie, Joseph and Anthony.
Gene Silencing by Polycomb ComplexesProf. Yi Zhang - University of North Carolina at Chapel Hill, USAYi Zhang is an Investigator of the Howard Hughes Medical Institute and Professor in the Lineberger Comprehensive Cancer Center and Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill. He earned an undergraduate degree and a MS at the College of Biological Sciences, Beijing Agricultural University, in the People's Republic of China. He received a PhD at the Institute of Molecular Biophysics of Florida State University in Tallahassee. He is an American Cancer Society Research Scholar and has won the Gertrude B. Elion Cancer Research Award from the American Association for Cancer Research and the Sidney Kimmel Foundation for Cancer Research Scholar Award.
Epigenetics: A Historical OverviewDr. Robin Holliday - National Institute for Medical Research, Mill Hill, London, UK Robin Holliday obtained his PhD at the University of Cambridge, England. He joined the scientific staff of the John Innes Institute, Bayfordbury, Hertford, in 1958, and there developed molecular models of genetic recombination. In experimental work he studied recombination and repair in the fungus Ustilago maydis and was the first to isolate and characterise mutants defective in these processes in any eukaryotic organism. He later moved to the National Institute for Medical Research at Mill Hill, London, and became head of the new Division of Genetics in 1970. He was elected Fellow of the Royal Society of London in 1976. He and his colleagues also studied possible mechanisms of the senescence of diploid human cells in culture, and their immortalisation. In 1975 he suggested with his student John Pugh that DNA methylation could be an important mechanism for the control of gene expression in higher organisms, and this has now become documented as a basic epigenetic mechanism in normal and also cancer cells. In 1988 he moved to a CSIRO laboratory in Sydney, Australia, where he continued to study ageing, and his book Understanding Ageing was published in 1995. The main focus of his experimental work was the epigenetic control of gene expression by DNA methylation in CHO cells. These experiments provide direct evidence that DNA methylation is a primary cause of gene silencing in mammalian cells.
Transcriptional elongation | Complexes involved | Mechanisms regulating rate and efficiency of elongation on chromatin templates
Discovery of the Polycomb group (PcG) of proteins | Role in embryogenesis | Species conservation | Latest developments in understanding molecular mechanism of gene silencing | Evidence on hierarchical recruitment
Introduction to epigenetics | the leading pioneers in the field of epigenetics | the basic features of development | switching and heritability of gene activities | DNA methylation | epimutations | differences between genetics and epigenetics | genomic imprinting | chromatin structure | histone modifications | the role of RNA in the epigenetic regulation of gene activity | the bisulfite sequencing technique | the epigenotype
Cytoplasmic Epigenetics: Proteins Acting as GenesDr. Reed Wickner - National Institutes of Health, USAReed B. Wickner has studied infectious diseases of Saccharomyces cerevisiae, including double-stranded RNA viruses, single-stranded RNA replicons and prions. He has used yeast genetics to define chromosomal genes affecting RNA virus replication.
Cytoplasmic Epigenetics: Inheritance by Cytoplasmic ContinuityProf. Philippe Silar - University of Paris, FranceProf. Philippe Silar is a Professor of Microbial Genetics at the University of Paris. His main research interest is focused on degenerative processes encountered during fungal vegetative growth as well as studying various aspects of fungal life cycles and biology. Prof. Silar presently coordinates an effort to sequence the genome of the filamentous fungus Podospora anserina. Dr. Fabienne Malagnac - University of Paris, FranceDr. Fabienne Malagnac is a Lecturer in Microbial Genetics at the University of Paris. His main research interest is focused on degenerative processes encountered during fungal vegetative growth as well as studying various aspects of fungal life cycles and biology.
A Historical Perspective on Ideas on X-Chromosome Inactivation Dr. Mary Lyon - Mammalian Genetics Unit, Medical Research Council, UKMary Lyon has a ScD degree from Cambridge University. She is the former head of the Genetics Division of the MRC Radiobiology Unit. She has over 200 publications on various aspects of mammalian genetics and is best known for her discovery of X-chromosome inactivation in mammals. She is a Fellow of the Royal Society and a Foreign Associate of the US Academy of Science, and has received various honours and awards for her work.
Prions (infectious proteins) include several self-propagating amyloids of S. cerevisiae and Podospora anserina and a self-activating enzyme of S. cerevisiae | these non-chromosomal genetic elements are genes composed of protein, just as nucleic acids can catalyse enzymatic reactions | the amyloid-based prions [PSI+] and [URE3] are diseases of yeast, but the [Het-s] prion of Podospora carries out a normal function for that organism, heterokaryon incompatibility
Description in microbes of heritable phenomena not based on nucleic acids | fundamental importance of these phenomena in fully understanding inheritance | transmittance through cellular continuity | molecular mechanisms | template assisted folding of macromolecular structures | self-perpetuating metabolic circuitry
The phenomenon of X-chromosome inactivation in female mammals | X-chromosome inactivation as a dosage compensation mechanism for equalising the dosage of X-linked gene products in XY males and XX females in somatic cells | inactivity of either the maternal or paternal X-chromosome in different cells in eutherian mammals | preferential inactivation of paternal X in the placenta of mice and in all cells of marsupials | initiation of the process from an X-inactivation centre | discovery of the key gene, Xist | the concept of initiation and maintenance of X-inactivation as separate processes | histone modifications and methylation of CpG islands as maintenance mechanisms | inactivation in autosomal and X-chromosomal DNA | LINE1s as booster elements on the X-chromosome
Genomic Imprinting: History and EmbryologyProf. Davor Solter - Max-Planck Institute of Immunobiology, GermanyDavor Solter obtained both his MD and PhD from the University of Zagreb, Croatia. He became Assistant and Associate Professor in the Departments of Anatomy and Biology, University Zagreb Medical School 1966-1973. In 1973 he moved to the Wistar Institute, Philadelphia, and became Member and Professor in 1981 as well as Wistar Professor at the University of Pennsylvania. In 1991 he was appointed Member of the Max-Planck Society and Director of the Max-Planck Institute of Immunobiology in Freiburg. He is also Adjunct Senior Staff Scientist at the Jackson Laboratory, Bar Harbor. He was and is a member of numerous editorial and advisory boards and of the American Academy of Arts and Sciences, EMBO and Academia Europea. In 1998 he received March of Dimes Prize in Developmental Biology for pioneering the concept of imprinting. Davor Solter contributed significantly to many areas of mammalian developmental biology, namely: differentiation of germ layers; role of cell surface molecules in regulating early development; biology and genetics of teratocarcinoma; biology of embryonic stem cells; imprinting and cloning. His current research interest focuses on the genetic and molecular control of genome reprogramming and of the activation of embryonic genome.
Genomic Imprinting and its RegulationDr. Anne Ferguson-Smith - University of Cambridge, UKDr. Anne Ferguson-Smith is a Reader in Developmental Genetics in the Department of Anatomy at the University of Cambridge. She conducts research into the role of genetic imprinting in normal mammalian development and disease states. Genomic imprinting causes some genes to be expressed solely from either maternally or paternally inherited chromosomes, and a number of disorders can arise when this process is disrupted. Her group is investigating the evolutionary origin of imprinting by examining the developmental impact of altering the gene dosage of imprinted genes on mouse chromosome twelve. Changes in gene dosage can be lethal to the developing embryo or cause a range of defects in the muscle, skeleton and placenta. The group has identified a number of imprinted genes on this chromosome and is studying their function in the development of mesoderm and placenta. Dr. Ferguson-Smith is also an Associate Member of the EU Epigenome network of excellence.
Epigenetic Regulation of PhenotypeProf. Emma Whitelaw - Queensland Institute of Medical Research, AustraliaEmma Whitelaw is a Senior Principal Research Fellow at Queensland Institute of Medical Research. After completing her undergraduate degree at the ANU, she obtained her PhD at Oxford. She has worked for the past twenty years on eukaryotic transcription using the mouse as a model organism. Emma's most notable research achievements are in the area of epigenetics and have largely come out of her work in Australia. In particular, her work on the transgenerational inheritance of epigenetic marks has stimulated interest in this area. After spending fourteen years at the University of Sydney, she is moving to a research institute to extend her work to address human health.
Emergence of imprinting as a concept from experiments involving reciprocal nuclear transfer in the mouse zygote | construction of embryos containing only the male genome (androgenones) or the female genome (gynogenones) | functional differences between male and female genomes necessitating that both be present to ensure normal development and establishing that these differences occur during gametogenesis by imprinting | identification and characterization of imprinted genes | initial experiments leading to the conceptualization of imprinting and its developmental consequences
Introduction to imprinting | classic embryological and genetic studies | identification and function of imprinted genes | imprinted domains and the organisation of imprinted clusters | epigenetic modifications and genome programming | cis-acting control at imprinted domains | DNA methylation and non-coding RNA | histone modifications | clinical implications
When does epigenetic reprogramming during the transfer of DNA between parents and their offspring occur, in the gametes or in early development? | inheritance of epigenetic marks can occur, meaning that information other than DNA sequence can be passed on from parent to offspring | the influence of parental environmental history on an individual's epigenetic state | does epigenetic inheritance have an adaptive value? | could epigenetic state be used to give a better estimate of disease risk?
Evolution of Mammal Epigenetic Control SystemsProf. Jenny Graves - Research School of Biological Sciences, The Australian National University, AustraliaJenny Graves obtained her PhD from the University of California, Berkeley. She built her career at La Trobe University in Melbourne, and recently moved to head the Comparative Genomics group at ANU and direct the ARC Centre for Kangaroo Genomics. Jenny Graves uses comparisons between genomes of humans and distantly related animals (Australia's kangaroos and platypus are a specialty) to understand how mammal genes and chromosomes evolved and how they function. Her laboratory uses this unique perspective to explore the origin, function and fate of human sex chromosomes, and to discover novel human genes and the sequences that control them.
RNAi and Heterochromatin in Plants and Fission YeastProf. Robert Martienssen - Cold Spring Harbor Laboratory, USADr. Martienssen completed his PhD at the Plant Breeding Institute at Cambridge University with Dr. David Baulcombe, and post-doctoral training with Drs. Bill Taylor and Mike Freeling at the University of California at Berkeley before joining the faculty at Cold Spring Harbor Laboratory in 1989, where he was appointed senior scientist and Professor in 1995. He has authored more than 120 papers in genetics and developmental biology. Dr. Martienssen has a longstanding interest in transposable elements (TEs), which were first discovered in maize by B. McClintock at Cold Spring Harbor. He demonstrated that the epigenetic regulation of genes when TEs integrate nearby strongly resembles, and may underlie heterochromatic position effect variegation. TEs constitute the majority of most genomes, especially in heterochromatic regions, and TE-based mechanisms may be responsible for genome-wide epigenetic regulation. Martienssen also maintains a strong interest in developmental biology, working with stem cell maintenance and organ polarity in plants. Key genes include the SANT domain gene ASYMMETRIC LEAVES1, and the cryptic RNase H gene ARGONAUTE1, which plays a central role in RNA interference (RNAi). The fission yeast Schizosaccharomyces pombe has only a single Argonaute gene, allowing Martienssen to demonstrate that RNAi is required for heterochromatic silencing and histone modifications in fission yeast, because heterochromatin (junk DNA) is transcribed but rapidly turned over by RNAi. Microarray analysis and large scale sequencing of small RNA has revealed that this process is conserved in plants, and is enhanced when repeats are arranged in tandem orientation. In 2003, Martienssen and co-authors were awarded the AAAS Newcomb-Cleveland prize for the 2002 Breakthrough of the Year in the magazine Science.
How, when and why did epigenetic silencing evolve in mammals? | examination of two mammal-specific systems, genomic imprinting and X-chromosome inactivation, from an evolutionary standpoint, using comparisons between humans, distantly related mammals (marsupials and monotremes) and other vertebrates | independent evolution of imprinting in different genomic regions and correlation with evolution of viviparity | step-wise evolution of the elements of the complex X-chromosome inactivation mechanism | shared features of imprinting and X-inactivation
Heterochromatin is composed of transposable elements (TEs) and related repeats | heterochromatic gene silencing and TE-mediated silencing are related and may be important in large genomes | tiling microarrays can be used to examine heterochromatic transcripts as well as DNA and histone modification | small interfering RNA (siRNA) corresponds to transposons and repeats | in plants TE siRNA depend on DNA methyltransferase MET1 and the SWI/SNF ATPase DDM1 which silence TEs via DNA and histone H3 lysine-9 (H3K9) methylation | in fission yeast and plants centromeric repeats are transcribed on one strand but rapidly turned over by RNA interference (RNAi) | RNAi of centromeric transcripts is required for transcriptional silencing of reporter genes | RNA polymerase II, the Argonaute (RITS) and RNA dependent RNA polymerase (RDRC) complexes are associated with heterochromatin and required for silencing | H3K9me2 depends on RNAi and on the Rik1-Clr4 complex | Clr4 is the histone H3K9 dimethyltransferase | Rik1 resembles both DNA and RNA binding proteins and is required for RNAi along with Clr4 | LTR retrotransposon silencing depends on histone deacetylation and silences pericentromeric repeats in Arabidopsis in addition to RNAi
RNAi and Heterochromatin in Plants and Fission Yeast Prof. Robert Martienssen - Cold Spring Harbor Laboratory, USADr. Martienssen completed his PhD at the Plant Breeding Institute at Cambridge University with Dr. David Baulcombe, and post-doctoral training with Drs. Bill Taylor and Mike Freeling at the University of California at Berkeley before joining the faculty at Cold Spring Harbor Laboratory in 1989, where he was appointed senior scientist and Professor in 1995. He has authored more than 120 papers in genetics and developmental biology. Dr. Martienssen has a longstanding interest in transposable elements (TEs), which were first discovered in maize by B. McClintock at Cold Spring Harbor. He demonstrated that the epigenetic regulation of genes when TEs integrate nearby strongly resembles, and may underlie heterochromatic position effect variegation. TEs constitute the majority of most genomes, especially in heterochromatic regions, and TE-based mechanisms may be responsible for genome-wide epigenetic regulation. Martienssen also maintains a strong interest in developmental biology, working with stem cell maintenance and organ polarity in plants. Key genes include the SANT domain gene ASYMMETRIC LEAVES1, and the cryptic RNase H gene ARGONAUTE1, which plays a central role in RNA interference (RNAi). The fission yeast Schizosaccharomyces pombe has only a single Argonaute gene, allowing Martienssen to demonstrate that RNAi is required for heterochromatic silencing and histone modifications in fission yeast, because heterochromatin (junk DNA) is transcribed but rapidly turned over by RNAi. Microarray analysis and large scale sequencing of small RNA has revealed that this process is conserved in plants, and is enhanced when repeats are arranged in tandem orientation. In 2003, Martienssen and co-authors were awarded the AAAS Newcomb-Cleveland prize for the 2002 Breakthrough of the Year in the magazine Science.
DNA Methylation and Genome Defense in Neurospora crassaProf. Eric Selker - Institute of Molecular Biology, University of Oregon, USAProf. Selker received his PhD from Stanford University in 1981 and did research in Germany and Wisconsin before joining the Institute of Molecular Biology, University of Oregon as an Assistant Professor in 1985. He was appointed Professor of Biology in 1997. His group is interested in how the eukaryotic genome is structured, how it functions and how it changes. They discovered the first known homology-dependent genome defense system (RIP) and are known for their elucidation of the control and function of DNA methylation in Neurospora. The Selker laboratory currently focuses primarily on mechanisms of gene silencing that involve alternative states of chromatin.
DNA MethylationProf. Adrian Bird - Wellcome Trust Centre for Cell Biology, University of Edinburgh, UKFollowing his PhD at Edinburgh University in 1970, Dr. Bird undertook postdoctoral research at the Universities of Yale and Zurich. In 1975 he returned to the MRC Mammalian Genome Unit in Edinburgh, where his research focused on DNA methylation and the existence of CpG islands as markers for mammalian genes. Following 3 years at the Institute for Molecular Pathology in Vienna, he moved back to Edinburgh as Buchanan Professor of Genetics in 1990. During this period he established a mechanistic connection between DNA methylation and chromatin via methyl-CpG binding proteins. His laboratory discovered the first such protein, MeCP2, and generated a mouse model for Rett Syndrome. Since 1995 Dr. Bird has been Director of the Wellcome Trust Centre for Cell Biology.
Heterochromatin is composed of transposable elements (TEs) and related repeats | heterochromatic gene silencing and TE-mediated silencing are related and may be important in large genomes | tiling microarrays can be used to examine heterochromatic transcripts as well as DNA and histone modification | small interfering RNA (siRNA) corresponds to transposons and repeats | in plants TE siRNA depend on DNA methyltransferase MET1 and the SWI/SNF ATPase DDM1 which silence TEs via DNA and histone H3 lysine-9 (H3K9) methylation | in fission yeast and plants centromeric repeats are transcribed on one strand but rapidly turned over by RNA interference (RNAi) | RNAi of centromeric transcripts is required for transcriptional silencing of reporter genes | RNA polymerase II, the Argonaute (RITS) and RNA dependent RNA polymerase (RDRC) complexes are associated with heterochromatin and required for silencing | H3K9me2 depends on RNAi and on the Rik1-Clr4 complex | Clr4 is the histone H3K9 dimethyltransferase | Rik1 resembles both DNA and RNA binding proteins and is required for RNAi along with Clr4 | LTR retrotransposon silencing depends on histone deacetylation and silences pericentromeric repeats in Arabidopsis in addition to RNAi
Control of DNA methylation | repeat-induced point (RIP) mutation | relationship of chromatin modifications and DNA methylation | mutants that eliminate DNA methylation | roles of histone H3 methyltransferase (DIM-5) and heterochromatin protein 1 (HP1) in DNA methylation | indications of involvement of protein acetylation, methylation and phosphorylation in mechanism of DNA methylation | propagation of DNA methylation and the associated silenced chromatin state
DNA methylation as an epigenetic mark | location and patterns of methylated and nonmethylated CpG sites in the vertebrate genome | factors determining DNA methylation patterns | association of DNA methylation with stable gene silencing, e.g. methylation of CpG islands on the inactive X-chromosome, ensures long term repression of associated genes | recruitment of corepressors that impose a silent chromatin structure | repulsion of transcriptional activators by methyl-CpG leading to gene silencing | the link between human disorders, including cancer, Rett Syndrome and ICF syndrome, and defects in the DNA methylation system
Polycomb Epigenetic Mechanisms Prof. Vincenzo Pirrotta - Department of Molecular Biology and Biochemistry, Rutgers University, USABorn in Palermo, Sicily, in 1942, Prof. Pirrotta migrated with his family to Rome and then to the US. He attended Harvard University as an undergraduate, graduate student and postdoctoral fellow, studying physical chemistry and molecular biology. He obtained his PhD with Matthew Meselson and Mark Ptashne and returned to Europe, moving progressively from Stockholm to Basel (Assistant Professor), to the new EMBL Laboratory in Heidelberg, studying gene regulation in bacteriophage lambda and then Drosophila molecular genetics. From Heidelberg, he moved to Houston, Texas, at the Baylor College of Medicine, studying developmental biology, gene regulation and chromatin organization. In 1992, when Prof. Pirrotta moved to the University of Geneva, he was researching the problems of chromatin silencing by the Polycomb proteins. He joined Rutgers University in the autumn of 2004 in pursuit of Polycomb silencing, chromatin complexes, genomics and nuclear architecture.
Histone Modifications and Prospects for an Epigenetic CodeProf. Bryan Turner - University of Birmingham Medical School, UKProf. Bryan Turner is Professor of Experimental Genetics at the University of Birmingham Medical School. He completed his PhD at the MRC Human Biochemical Genetics Unit, The Galton Laboratory, University College London in 1973, then moved to the Department of Clinical Genetics at Mount Sinai School of Medicine, New York. In 1978 he joined the National Institute for Medical Research, Mill Hill, where he stayed until his move to the University of Birmingham Medical School in 1981. He now heads the Chromatin and Gene Expression Group in the new Institute of Biomedical Research. Prof. Turner is a Fellow of the Academy of Medical Sciences and a Member of the European Molecular Biology Organization (EMBO).
Epigenetic Control by Histone MethylationProf. Thomas Jenuwein - Research Institute of Molecular Pathology (IMP), AustriaProf. Jenuwein is Senior Scientist at the Research Institute of Molecular Pathology (IMP), Vienna, and Adjunct Professor at the Institute of Microbiology and Genetics at the University of Vienna. His research focuses on the functional characterization of mammalian chromatin and his team identified the first histone lysine methyltransferase (HMTase) and showed that the selective methylation of histone H3 on the lysine 9 residue (H3-K9) generates a high-affinity binding site for the chromo-domain of the HP1 proteins. These landmark findings established a biochemical explanation for the formation and propagation of silenced chromatin domains and for the functional organization of chromosomes. Together, they represent important breakthroughs in chromatin research during the last years. Prof. Jenuwein is an Elected Member of EMBO, a Member of Faculty of 1000, the coordinator of the GEN-AU network "Epigenetic plasticity of the mammalian genome" and the coordinator of the European Network of Excellence (NoE) "The Epigenome" and was awarded an Honorary Professorship at the University of Vienna in 2003 and the Sir Hans Krebs Medal of the FEBS society in July 2005.
Polycomb Group (PcG) mechanisms as regulators of Drosophila homeotic genes | multiprotein complexes | histone methylation and the Polycomb chromodomain | Polycomb Response Elements (PREs) | understanding of the PcG protein distribution, promoter silencing properties and the genomic targets of PcG regulation | involvement of PcG mechanisms in stem cell maintenance, proliferation, differentiation and mammalian X-chromosome inactivation
Enzyme-catalyzed modification of the N-terminal tail domains of core histones provides an array of marks across the nucleosome surface and a source of epigenetic information | this information influences protein-protein interactions during short-term regulation of ongoing transcription and is a means of maintaining or modifying patterns of gene expression from one cell generation to the next | cellular memory | histone modifications may constitute a heritable epigenetic code that acts in concert with the genetic code as a long-term regulator of gene expression
The diversity of covalent histone tail modifications for imparting epigenetic information | observations of robust histone modifications at silent chromatin regions | the representation of repressive histone marks as indications of epigenetic plasticity in different cells | analysis of the profiles of normal and aberrant histone lysine methylation patterns, as they occur during the transition of an embryonic to a differentiated cell or in controlled self-renewal vs. pro-neoplastic or metastatic conditions | elucidation of these histone modification patterns for novel advances in stem cell research, nuclear reprogramming and cancer