Recruitment and biological consequences of histone modification of H3K27me3 and H3K9me3

Abstract

Two histone marks, H3K27me3 and H3K9me3, are well known for their repressive roles in the genic and nongenic regions of metazoan genomes. Several protein complexes are known to be responsible for generating these marks, including polycomb repression complex 2 and several H3K9 methylases. Recent studies have shown that the targeting of these histone-modifying complexes within mammalian genomes may be mediated through several DNA-binding proteins, including AEBP2, JARID2, and YY1. In this review, we discuss the potential targeting mechanisms in light of the recent results that have been derived from genome-wide chromatin immunoprecipitation sequencing data and the in vivo functions of these two histone marks in light of the results derived from mouse and human genetic studies.

Keywords: AEBP2; H3K27me3; H3K9me3; JARID2; PRC2; YY1.

Figure 1

Potential targeting mechanisms for polycomb repression complex 2 (PRC2) and H3K9 methylases. The CpG-rich promoters of development regulators are first recognized by AEBP2 and/or JARID, and subsequently PRC2 is recruited to these target loci, resulting in trimethylation on H3K27. In contrast, the tandem repeats or retrotransposons are first recognized by YY1 and transcribed by Pol II. The repeat-driven transcripts are further processed and later used for the targeting of H3K9 methylases, resulting in trimethylation on H3K9 in the tandem repeats and retrotransposons. Once a given genomic region is marked by H3K27me3 or H3K9me3, that region becomes transcriptionally silent by a series of other follow-up events, including recruitment of PRC1 (H3K27me3) and HP1 (H3K9me3).