BME 130 – Genomes

Lecture 19

The histone code

Figure 7.1 Genomes 3 (© Garland Science 2007)

Figure 10.13 Genomes 3 (© Garland Science 2007)

H3H4H2AH2B

CHiP-Seq

DNADNA-binding proteins

(histones, e.g)

crosslink

Immuno-precipitate and fragment DNA

Immuno-precipitateand fragment DNA

Reverse cross-links and sequence

ChIP-Seq and ChIP-chip comparison of two histone marks

Lower background & tighter peaks in ChIP-Seq (better contrast)

trxG(activation)

PcG(repression)

Promoter classeshigh CpG

gene

gene

genelow CpG

intermediate CpG

CpG

Highly expressed, housekeeping genes; other genesN=11,410

Genes with high tissue-specificityN=3,014

Mixture of genesN=3,338

NPC=neural progenitor cells MEF=embryonic fibroblastsES = embryonic stem cells

Highly dynamic histone modification during differentiation

H3K36me3 marks gene bodies (may prevent aberrant transcriptional initiation)

Imprinting is reflected in H3K36me3 state

Nucleosome positioning and gene structure

Histone modification in cell division

HaspinH3 H3

P

H3 H3PSu

rviv

in

Chr

omos

omal

pass

enge

r

com

plex A

uro

raB

(kin

ase)