outline nucleosome distribution chromatin modification patterns mechanisms of chromatin...
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Outline
Nucleosome distribution Chromatin modification patterns Mechanisms of chromatin modifications Biological roles
Chromatin modifications
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)
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
Barski et al., Cell 2007 vol. 129 (4) pp. 823-837
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.
Hawkins et al., Cell Stem Cell 2010
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
Chromatin modifications demarcate functional elements in the genome
Zhou, Goren and Bernstein, Nature Rev Genetics, 2011
Outline
Nucleosome distribution Chromatin modification patterns Mechanisms of chromatin modifications Biological roles
Histone acetylation reaction
HAT Characteristics
HDAC Complexes
De Ruijter, et al. Biochem J. (2002)
Histone Methylation (lysine)
Both activation and repression
More stable HKMT HKDM
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.
Bromodomain recognizes K-ac
Bromodomain and lysine acetylation
Chromodomain and lysine methylation
Positional Effect Variegation in Fly
Allis et al., Epigenetics, CSHL Press
Euchromatin and Heterochromatin
Allis et al., Epigenetics, CSHL Press
Screening for modifiers of PEV
Allis et al., Epigenetics, CSHL Press
Allis et al., Epigenetics, CSHL Press
H3K27me3 and Polycomb Complexes
Model for PcG silencing in cellular memory
Methylation of Histone H3K4
Rothenburg et al., Molecular Cell 2006
Histone Demethylases
Outline
Nucleosome distribution Chromatin modification patterns Mechanisms of chromatin modifications Biological roles
Two different views on the propagation of cellular memory
Bonasio et al. Science 2010, 330 pp. 612-6
Transmission of epigenetic states