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