Role of remodeling and spacing factor 1 in histone H2A ubiquitination mediated gene silencing

ABSTRACT: Posttranslational modification of histones plays important roles in regulating chromatin-based nuclear processes. Histone H2A ubiquitination (H2Aub) is a prevalent modification and has been primarily linked to gene silencing; however, the mechanism by which H2Aub represses gene expression remains largely unclear. Here we report the identification of RSF1 (remodeling and spacing factor 1), a subunit of the RSF (remodeling and spacing factor) complex, as a novel H2Aub binding protein which mediates the repressive function of H2Aub on gene expression. RSF1 preferentially associates with H2Aub nucleosomes through a previously uncharacterized region designated as the ubiquitinated H2A binding (UAB) motif. RSF1 interacts with H2Aub nucleosomes specifically and the UAB motif is required for RSF1 to interact with H2Aub nucleosomes in vitro and in vivo. Genes regulated by RSF1 overlap significantly with genes regulated by RNF2 or Ring1B, the catalytic subunit of Polycomb repressive complex 1, in both human and mouse cells. RSF1 binds to gene promoter regions, and over 92% of H2Aub enriched genes, including the classic PRC1 target Hox genes, are co-bound by RSF1. Reduction of H2Aub levels by Ring1B knockout results in a significant reduction of RSF1 binding. RSF1 knockout does not affect RNF2/Ring1B or H2Aub levels but results in re-expression of H2Aub target genes, accompanied by a reduction in the spacing and stability of H2Aub nucleosomes. The direct role of RSF1 in repressing H2Aub target gene expression is further demonstrated by chromatin based in vitro transcription assay. Finally, RSF1 regulates Xenopus early embryonic development and gene expression in a fashion similar to that of PRC1 subunit Ring1A. Therefore, this study identifies RSF1 as a novel H2Aub binding protein and reveals that RSF1 contributes to H2Aub mediated gene silencing by maintaining a regular spaced, stable nucleosome array at promoter regions.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE93090 | GEO | 2018/02/16

REPOSITORIES: GEO