chromatin structure and remodeling in eukaryotic cells
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Lecture 3. Chromatin structure and remodeling in eukaryotic cells. H2A , H2B , H3 and H4. Felsenfeld & Groudine , Nature 2003. Outline. Nucleosome distribution Chromatin modification patterns Mechanisms of chromatin modifications Biological roles. Nucleosomes. - PowerPoint PPT PresentationTRANSCRIPT
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Chromatin structure and remodeling in eukaryotic cells
Lecture 3
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Felsenfeld & Groudine, Nature 2003
H2A , H2B , H3 and H4
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Outline Nucleosome distribution Chromatin modification patterns Mechanisms of chromatin modifications Biological roles
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Nucleosomes The formation of chromatin
through the binding of histones to DNA allows the DNA to be folded into chromosomes and compacted by as much as a factor of 10,000.
Packaging of DNA into nucleosomes obstructs access to DNA by transcription factors and other nuclear machinery
But it also provides opportunities for these factors to access specific regions of the genes (such as TSS) more quickly
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Nucleosome composition
H2A , H2B , H3 and H4
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Cizhong Jiang, B Franklin Pugh, Nature Review Genetics, 2009 vol. 10 (3) pp. 161-72
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The presence of NFRs demonstrated that open promoter states are stable and common, even at genes that are transcribed so infrequently
Genomic distribution of nucleosomes
Cizhong Jiang, B Franklin Pugh, Nature Review Genetics, 2009 vol. 10 (3) pp. 161-72
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Nucleosome spacing is regulated by chromatin remodeling factors such as ISWI and linker histone H1
Nucleosome spacing in different species may differ (185bp in human, 165 in yeast)
Cizhong Jiang, B Franklin Pugh, Nature Review Genetics, 2009 vol. 10 (3) pp. 161-72
Phasing and rotational position of nucleosomes
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Nucleosome spacing is regulated by chromatin remodeling factors such as ISWI and linker histone H1
Nucleosome spacing in different species may differ (185bp in human, 165 in yeast)
Nucleosome position patterns in vivo is likely driven by a combination of random positioning and statistical positioning
Cizhong Jiang, B Franklin Pugh, Nature Review Genetics, 2009 vol. 10 (3) pp. 161-72
Phasing and rotational position of nucleosomes
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Outline Nucleosome distribution Chromatin modification patterns Mechanisms of chromatin modifications Biological roles
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A method to map nucleosome position at base resolution
Brogaard,…, Widom, Nature 2012, 486 (7404) pp. 496-501
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Global features of nucleosome positioning
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Distribution of linker DNA lengths
Length ~ 10n + 5bp What could this mean for the higher order chromatin structure?
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Chromatin modifications
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Profiling chromatin marks in the genome
ChIP-chip or ChIP-seq analysis is a general approach for mapping chromatin modifications in the genome
It is critical to use specific antibodies
Typically a lot of cells are needed (10^6)
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Profiling chromatin marks in the genome
ChIP-chip or ChIP-seq analysis is a general approach for mapping chromatin modifications in the genome
It is critical to use specific antibodies
Typically a lot of cells are needed (10^6)
Park PJ. Nature Reviews Genetics 10, 669-680
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Barski et al., Cell 2007 vol. 129 (4) pp. 823-837
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The consortium homepage: http://epigenomebrowser.org All protocols in use can be found here, as well as information about quality metrics, news,
publications, general program information, and links to other associated websites.
Producing a public resource of human epigenomic data to catalyze basic biology and disease-oriented research. Mapping DNA methylation, histone modifications, chromatin accessibility and RNA transcripts in stem cells and primary ex vivo tissues selected to represent the normal counterparts of tissues and organ systems frequently involved in human disease. Rapid release of raw sequence data, profiles of epigenomic features and higher-level integrated maps.
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Hawkins et al., Cell Stem Cell 2010
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Characteristic patterns of chromatin modification exist at promoters and enhancers
Enhancers are marked by H3K4me1 but NOT H3K4me3 Promoters are marked by H3K4me3 and a depletion of H3K4me1
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Chromatin modifications demarcate functional elements in the genome
Zhou, Goren and Bernstein, Nature Rev Genetics, 2011
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Outline Nucleosome distribution Chromatin modification patterns Mechanisms of chromatin modifications Biological roles
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Histone acetylation reaction
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HAT Characteristics
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HDAC Complexes
De Ruijter, et al. Biochem J. (2002)
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Histone Methylation (lysine) Both activation
and repression More stable HKMT HKDM
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Histone Demethylases
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Two models of histone modifications’ roles Histone modifications could directly alter
chromatin folding. Modified histone residues could alter the
ability of histones to recruit non-histone preotinrs to chromatin, which in turn alter the abiligy of the transcriptional machinery to recognize the template.
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Bromodomain recognizes K-ac
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Bromodomain and lysine acetylation
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Chromodomain and lysine methylation
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Outline Nucleosome distribution Chromatin modification patterns Mechanisms of chromatin modifications Biological roles
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Two different views on the propagation of cellular memory
Bonasio et al. Science 2010, 330 pp. 612-6
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Transmission of epigenetic states
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