Chromatin Environment of Histone Variant H3.3 Revealed by Quantitative Imaging and Genome-scale Chromatin and DNA Immunoprecipitation

被引:41
作者
Delbarre, Erwan
Jacobsen, Bente Marie
Reiner, Andrew H.
Sorensen, Anita L.
Kuntziger, Thomas
Collas, Philippe [1 ]
机构
[1] Univ Oslo, Inst Basic Med Sci, Fac Med, N-0317 Oslo, Norway
关键词
EMBRYONIC STEM-CELLS; ACTIVE CHROMATIN; GENE-EXPRESSION; CHIP-CHIP; METHYLATION; MARKS; REPLACEMENT; DEPOSITION; DIFFERENTIATION; TRANSCRIPTION;
D O I
10.1091/mbc.E09-09-0839
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In contrast to canonical histones, histone variant H3.3 is incorporated into chromatin in a replication-independent manner. Posttranslational modifications of H3.3 have been identified; however, the epigenetic environment of incorporated H3.3 is unclear. We have investigated the genomic distribution of epitope-tagged H3.3 in relation to histone modifications, DNA methylation, and transcription in mesenchymal stem cells. Quantitative imaging at the nucleus level shows that H3.3, relative to replicative H3.2 or canonical H2B, is enriched in chromatin domains marked by histone modifications of active or potentially active genes. Chromatin immunoprecipitation of epitope-tagged H3.3 and array hybridization identified 1649 H3.3-enriched promoters, a fraction of which is coenriched in H3K4me3 alone or together with H3K27me3, whereas H3K9me3 is excluded, corroborating nucleus-level imaging data. H3.3-enriched promoters are predominantly CpG-rich and preferentially DNA methylated, relative to the proportion of methylated RefSeq promoters in the genome. Most but not all H3.3-enriched promoters are transcriptionally active, and coenrichment of H3.3 with repressive H3K27me3 correlates with an enhanced proportion of expressed genes carrying this mark. H3.3-target genes are enriched in mesodermal differentiation and signaling functions. Our data suggest that in mesenchymal stem cells, H3.3 targets lineage-priming genes with a potential for activation facilitated by H3K4me3 in facultative association with H3K27me3.
引用
收藏
页码:1872 / 1884
页数:13
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