Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

L3MBTL2 protein acts in concert with PcG protein mediated monoubiquitination of H2A to establish a repressive chromatin structure [ChIP-Seq data].

ABSTRACT: Human MBT domain-containing protein L3MBTL2 was found to be an integral component of a protein complex that we termed Polycomb Repressive Complex 1-like 3 (PRC1L3) given the presence of the PcG proteins RING1, RING2 and PCGF6. L3MBTL2 binds chromatin in a histone modification-independent manner and is required for the repressive function of PRC1L3. PRC1L3 also contains E2F6 and CBX3, two factors with wellM-bM-^@M-^Pestablished functions in transcriptional repression. GenomeM-bM-^@M-^Pwide profiling identified several hundred genes that are simultaneously bound by L3MBTL2 and E2F6, preferentially around transcriptional start sites. Importantly, these genes are largely distinct from those targeted by other E2Fs or L3MBTL, another MBTM-bM-^@M-^Pdomain containing protein that interacts with RB1. H3K27 or H3K9 methylation, two chromatin modifications implicated in gene silencing, are not present on all L3MBTL2 target genes. L3MBTL2-specific RNAi results in altered target gene expression patterns and affects the differentiation program of hematopoietic cells. Our data suggest that repression of transcription via chromatin modulation, reflective of PRC1 function, can be achieved by multiple players and does not necessarily require the presence of histone lysine methylation marks. 7 total ChIP-seq datasets; one L3MBTL2 dataset done in duplicate in K562 cells; one E2F6 dataset done in duplicate in K562 cells; one H3K27me3 replicate dataset in K562 cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Philip Cayting

PROVIDER: E-GEOD-28162 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

L3MBTL2 protein acts in concert with PcG protein-mediated monoubiquitination of H2A to establish a repressive chromatin structure.

Trojer Patrick P Cao Alina R AR Gao Zhonghua Z Li Yan Y Zhang Jin J Xu Xiaoqin X Li Guohong G Losson Regine R Erdjument-Bromage Hediye H Tempst Paul P Farnham Peggy J PJ Reinberg Danny D

Molecular cell 20110501 4

We have identified human MBT domain-containing protein L3MBTL2 as an integral component of a protein complex that we termed Polycomb repressive complex 1 (PRC1)-like 4 (PRC1L4), given the copresence of PcG proteins RING1, RING2, and PCGF6/MBLR. PRC1L4 also contained E2F6 and CBX3/HP1γ, known to function in transcriptional repression. PRC1L4-mediated repression necessitated L3MBTL2 that compacted chromatin in a histone modification-independent manner. Genome-wide location analyses identified seve ...[more]

PMID: 21596310

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Project description:Only a small percentage of human transcription factors (e.g. those associated with a specific differentiation program) are expressed in a given cell type. Thus, cell fate is mainly determined by cell type-specific silencing of transcription factors that drive different cellular lineages. Several histone modifications have been associated with gene silencing, including H3K27me3 and H3K9me3. We have previously shown that the two largest classes of mammalian transcription factors are marked by distinct histone modifications; homeobox genes are marked by H3K27me3 and zinc finger genes are marked by H3K9me3. Several histone methyltransferases (e.g. G9a and SETDB1) may be involved in mediating the H3K9me3 silencing mark. We have used ChIP-chip (GSE24480) and ChIP-seq to demonstrate that SETDB1, but not G9a, is associated with regions of the genome enriched for H3K9me3. A current model is that SETDB1 is recruited to specific genomic locations via interaction with the corepressor TRIM28 (KAP1), which is in turn recruited to the genome via interaction with zinc finger transcription factors that contain a Kruppel-associated box (KRAB) domain. However, specific KRAB-ZNFs that recruit TRIM28 (KAP1) and SETDB1 to the genome have not been identified. We now show that ZNF274 (a KRAB-ZNF that contains 5 C2H2 zinc finger domains), can interact with KAP1 in vitro and, using ChIP-seq, we show that ZNF274 binding sites co-localize with SETDB1, KAP1, and H3K9me3 at the 3’ ends of zinc finger genes. Knockdown of ZNF274 with siRNAs reduced the levels of KAP1 and SETDB1 recruitment to the binding sites. These studies provide the first identification of a KRAB domain-containing ZNFs that is involved in recruitment of the KAP1 and SETDB1 to the human genome. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf 7 total ChIP-seq datasets; 4 ZNF274 datasets done in duplicate from 4 different cell lines; 1 KAP1 duplicate dataset done in duplicate from K562 cells; 1 SetDB1 duplicate dataset from K562 cells; 1 H3K9me3 duplicate dataset from K562 cells

Dataset Information

L3MBTL2 protein acts in concert with PcG protein mediated monoubiquitination of H2A to establish a repressive chromatin structure [ChIP-Seq data].

Publications

L3MBTL2 protein acts in concert with PcG protein-mediated monoubiquitination of H2A to establish a repressive chromatin structure.

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