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BRG1 recruitment by transcription factors MITF and SOX10 defines a specific configuration of regulatory elements in the melanocyte lineage

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Patrick Laurette

PROVIDER: E-GEOD-61967 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells.

Laurette Patrick P Strub Thomas T Koludrovic Dana D Keime Céline C Le Gras Stéphanie S Seberg Hannah H Van Otterloo Eric E Imrichova Hana H Siddaway Robert R Aerts Stein S Cornell Robert A RA Mengus Gabrielle G Davidson Irwin I

eLife 20150324

Microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage. To understand how MITF regulates transcription, we used tandem affinity purification and mass spectrometry to define a comprehensive MITF interactome identifying novel cofactors involved in transcription, DNA replication and repair, and chromatin organisation. We show that MITF interacts with a PBAF chromatin remodelling complex comprising BRG1 and CHD7. BRG1 is essential for melanoma cell pr ...[more]

PMID: 25803486

Similar Datasets

BRG1 recruitment by transcription factors MITF and SOX10 defines a specific configuration of regulatory elements in the melanocyte lineage (RNA-seq)

Project description:Microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage. By tandem affinity purification and mass spectrometry, we present a comprehensive characterisation of the MITF interactome comprising multiple novel cofactors involved in transcription, DNA replication and repair and chromatin organisation, including a BRG1 chromatin remodelling complex comprising CHD7. BRG1 is essential for melanoma cell proliferation in vitro and for normal melanocyte development in vivo. MITF and SOX10 actively recruit BRG1 to a set of MITF-associated regulatory elements (MAREs) at active enhancers. MITF, SOX10 and YY1 bind between two BRG1-occupied nucleosomes thus defining both a combinatorial signature of transcription factors essential for the melanocyte lineage and a specific chromatin organisation of MAREs. Nevertheless, BRG1 silencing enhances MITF occupancy at MAREs showing that BRG1 acts to promote dynamic MITF interactions with chromatin. 19 samples corresponding to mRNA profiles of 501Mel and Hermes3A after MITF, BRG1 or control shRNA-mediated knockdown were generated by deep sequencing in triplicate (in duplicate for 501_shMITF and corresponding control 501_shSCR2), using HiSeq2500.

2015-04-02 | E-GEOD-61966 | biostudies-arrayexpress

TAF4 promotes pre-initiation complex formation and HNF4A occupancy of regulatory elements required to activation post-natal gene expression programme in hepatocytes (RNA-seq)

Project description:The nuclear receptor HNF4A regulates embryonic and post-natal hepatocyte gene expression. Using hepatocyte-specific inactivation in mice, we show that the TAF4 subunit of TFIID acts as a cofactor for HNF4A in vivo and that HNF4A interacts directly with the TAF4-TAF12 heterodimer in vitro. In vivo, TAF4 is required to maintain HNF4A-directed embryonic gene expression at post-natal stages and for HNF4A-directed activation of post-natal gene expression. TAF4 promotes HNF4A occupancy of functional cis-regulatory elements located adjacent to the transcription start sites of post-natal expressed genes and for pre-initiation complex formation required for their expression. Promoter-proximal HNF4A-TFIID interactions are therefore required for pre-initiation complex formation and stable HNF4A occupancy of regulatory elements as two concomitant mutually dependent processes. RNA profiles in wild-type and Taf4-/- livers by deep sequencing

2014-09-25 | E-GEOD-57712 | biostudies-arrayexpress

TAF4 promotes pre-initiation complex formation and HNF4A occupancy of regulatory elements required to activation post-natal gene expression programme in hepatocytes

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-09-25 | E-GEOD-57814 | biostudies-arrayexpress

VL30 retro-transposons are TRIM24-repressed enhancers that generate non-coding RNA to regulate gene expression in mouse hepatocytes. [RNA-Seq]

Project description:TRIM24 and TRIM33 interact to form a corepressor complex that suppresses murine hepatocellular carcinoma (HCC). TRIM24 and TRIM33 cooperatively repress retinoic acid receptor dependent activity of VL30 retro-transposons in hepatocytes in vivo. In TRIM24 knockout hepatocytes, VL30 long terminal repeats (LTRs) generate enhancer (e)RNAs and act as surrogate promoter and enhancer elements deregulating expression of neighbouring genes. We show that a VL30 LTR-derived eRNA is essential to activate the lipocalin 13 gene in hepatocytes in vivo. A further consequence of VL30 de-repression is the accumulation of retro-transcribed VL30 DNA in the cytoplasm of TRIM24-mutant hepatocytes and activation of the viral defence/interferon response. VL30 activation therefore modulates gene expression via the enhancer activity of the LTRs and by activation of the interferon response. Both of these processes are genetically linked to HCC development suggesting that VL30 repression by TRIM24 plays an important role in tumour suppression. RNA profiles in liver of wild type (WT) and Trim24-/- mice by deep sequencing using Illumina GAIIx.

2013-01-01 | E-GEOD-39851 | biostudies-arrayexpress

VL30 retro-transposons are TRIM24-repressed enhancers that generate non-coding RNA to regulate gene expression in mouse hepatocytes.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-01-01 | E-GEOD-39853 | biostudies-arrayexpress

BRG1 recruitment by transcription factors MITF and SOX10 defines a specific configuration of regulatory elements in the melanocyte lineage (ChIP-seq)

Project description:Microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage. By tandem affinity purification and mass spectrometry, we present a comprehensive characterisation of the MITF interactome comprising multiple novel cofactors involved in transcription, DNA replication and repair and chromatin organisation, including a BRG1 chromatin remodelling complex comprising CHD7. BRG1 is essential for melanoma cell proliferation in vitro and for normal melanocyte development in vivo. MITF and SOX10 actively recruit BRG1 to a set of MITF-associated regulatory elements (MAREs) at active enhancers. MITF, SOX10 and YY1 bind between two BRG1-occupied nucleosomes thus defining both a combinatorial signature of transcription factors essential for the melanocyte lineage and a specific chromatin organisation of MAREs. Nevertheless, BRG1 silencing enhances MITF occupancy at MAREs showing that BRG1 acts to promote dynamic MITF interactions with chromatin. 8 samples corresponding to genomic occupancy profiling of MITF, SOX10, BRG1 after si-control, BRG1 after si-MITF and BRG1 after siSOX10; and their respective controls (MITF Input, SOX10 Input, GFP-siCTRL ChIPseq) in 501Mel cells.

2015-04-02 | E-GEOD-61965 | biostudies-arrayexpress

Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington's disease

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-04-01 | E-GEOD-59572 | biostudies-arrayexpress

High-Resolution Profiling of Novel Transcribed Regions During Rat Spermatogenesis

Project description:Mammalian spermatogenesis is a complex and highly orchestrated combination of processes in which male germline proliferation and differentiation result in the production of mature spermatozoa. If recent genome-wide studies have contributed to the in-depth analysis of the male germline protein-coding transcriptome, little effort has yet been devoted to the systematic identification of novel unannotated transcribed regions expressed during mammalian spermatogenesis. We report high-resolution expression profiling of male germ cells in the rat using Illumina next-generation sequencing technology and highly enriched testicular cell populations. Among 20,424 high-confidence transcripts reconstructed, we defined a stringent set of 1,419 long multi-exonic unannotated transcripts expressed in the testis, named TUTs. These were classified into seven groups with different expression patterns. The vast majority of TUTs share many of the characteristics of vertebrate long non-coding RNAs (lncRNAs). We also markedly reinforced the finding that TUTs and known lncRNAs accumulate during the meiotic and postmeiotic stages of spermatogenesis in mammals, and that X-linked meiotic TUTs do not escape the silencing effects of meiotic sex chromosome inactivation. Importantly, we discovered that TUTs and known lncRNAs with a peak expression during meiosis define a distinct class of non-coding transcripts that exhibit exons twice as long as those of other transcripts. Our study provides new insights in transcriptional profiling of the male germline and represents a high-quality resource of novel loci expressed during spermatogenesis that significantly contributes to the rat genome annotation. A graphical display of the data is conveniently accessible through the ReproGenomics Viewer (RGV) at http://rgv.genouest.org. Genome-wide expression profiling analysis using Illumina next-generation sequencing technology

2014-06-01 | E-GEOD-48321 | biostudies-arrayexpress

Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington’s disease [ChIP-seq]

Project description:Huntington neurodegenerative disease (HD) is associated with extensive down-regulation of neuronal genes. We show preferential down-regulation of super-enhancer-regulated neuronal function genes in the striatum of HD mice. Striatal super-enhancers display extensive H3K27 acetylation within gene bodies and drive transcription characterized by low levels of paused RNAPII. Down-regulation of gene expression is associated with diminished H3K27 acetylation and RNAPII recruitment. Striatal super-enhancers are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Thus, enhancer topography and transcription dynamics are major parameters determining the propensity of a gene to be deregulated in a neurodegenerative disease. Examination of H3k27ac and RNA pol II in Striatum by deep sequencing

2015-04-01 | E-GEOD-59570 | biostudies-arrayexpress

Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington’s disease [RNA-seq]

Project description:Huntington neurodegenerative disease (HD) is associated with extensive down-regulation of neuronal genes. We show preferential down-regulation of super-enhancer-regulated neuronal function genes in the striatum of HD mice. Striatal super-enhancers display extensive H3K27 acetylation within gene bodies and drive transcription characterized by low levels of paused RNAPII. Down-regulation of gene expression is associated with diminished H3K27 acetylation and RNAPII recruitment. Striatal super-enhancers are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Thus, enhancer topography and transcription dynamics are major parameters determining the propensity of a gene to be deregulated in a neurodegenerative disease. RNA profiles in Striatum of WT and R6/1 mice by deep sequencing using Illumina HiSeq 2000.

2015-04-01 | E-GEOD-59571 | biostudies-arrayexpress

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