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Series GSE93090 Query DataSets for GSE93090
Status Public on Feb 16, 2018
Title Role of remodeling and spacing factor 1 in histone H2A ubiquitination mediated gene silencing
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
Overall design Examination of binding pattern of RSF1, gene expression profiles and nucleosome position in wildtype and RSF1 knock out mouse embryonic stem cells. And binding pattern of RSF1 and gene expression profiles in wildtype and RSF1 knock down HeLa cells.
Contributor(s) Zhang Z, Jones AE, Wu W, Kim J, Kang Y, Bi X, Gu Y, Renfrow MB, Vassylyeva MN, Vassylyev D, Giles KE, Chen D, Tong Y, Liu CF, An W, Chang C, Luo J, Wang H
Citation(s) 28855339
Submission date Jan 03, 2017
Last update date May 15, 2019
Contact name Hengbin Wang
Phone 2059345286
Organization name University of Alabama at Birmingham
Department Biochemistry and Molecular Genetics
Lab Hengbin Wang
Street address 720 20th St S Kaul Bldg 430
City Birmingham
State/province AL
ZIP/Postal code 35294
Country USA
Platforms (3)
GPL9250 Illumina Genome Analyzer II (Mus musculus)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (13)
GSM2443533 HeLa_RSF1_KD_RNA-seq
GSM2443534 HeLa_RNF2_KD_RNA-seq
GSM2443535 HeLa_control_RNA-seq
BioProject PRJNA359934
SRA SRP095955

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE93090_HeLa_RNA-seq_FPKM.txt.gz 296.9 Kb (ftp)(http) TXT
GSE93090_RAW.tar 1.8 Gb (http)(custom) TAR (of WIG)
GSE93090_mESC_RNA-seq_FPKM.txt.gz 291.7 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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