Immunostaining of modified histones defines high-level features of the human metaphase epigenome.

Abstract:

BACKGROUND:Immunolabeling of metaphase chromosome spreads can map components of the human epigenome at the single cell level. Previously, there has been no systematic attempt to explore the potential of this approach for epigenomic mapping and thereby to complement approaches based on chromatin immunoprecipitation (ChIP) and sequencing technologies. RESULTS:By immunostaining and immunofluorescence microscopy, we have defined the distribution of selected histone modifications across metaphase chromosomes from normal human lymphoblastoid cells and constructed immunostained karyotypes. Histone modifications H3K9ac, H3K27ac and H3K4me3 are all located in the same set of sharply defined immunofluorescent bands, corresponding to 10- to 50-Mb genomic segments. Primary fibroblasts gave broadly the same banding pattern. Bands co-localize with regions relatively rich in genes and CpG islands. Staining intensity usually correlates with gene/CpG island content, but occasional exceptions suggest that other factors, such as transcription or SINE density, also contribute. H3K27me3, a mark associated with gene silencing, defines a set of bands that only occasionally overlap with gene-rich regions. Comparison of metaphase bands with histone modification levels across the interphase genome (ENCODE, ChIP-seq) shows a close correspondence for H3K4me3 and H3K27ac, but major differences for H3K27me3. CONCLUSIONS:At metaphase the human genome is packaged as chromatin in which combinations of histone modifications distinguish distinct regions along the euchromatic chromosome arms. These regions reflect the high-level interphase distributions of some histone modifications, and may be involved in heritability of epigenetic states, but we also find evidence for extensive remodeling of the epigenome at mitosis.

journal_name

Genome Biol

journal_title

Genome biology

authors

Terrenoire E,McRonald F,Halsall JA,Page P,Illingworth RS,Taylor AM,Davison V,O'Neill LP,Turner BM

doi

10.1186/gb-2010-11-11-r110

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

R110

issue

11

eissn

1474-7596

issn

1474-760X

pii

gb-2010-11-11-r110

journal_volume

11

pub_type

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