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Trithorax-group protein ASH1 defines novel H3K36me3/H3K9me3 bivalent domains

ABSTRACT: A Trithorax-group (TrxG) protein ASH1 selectively dimethylates histone H3 lysine 36 (H3K36) and is required for expression of Hox genes. Genome-wide targets and molecular functions of ASH1, however, have remained elusive. Here we report ChIP-seq analysis of ASH1 targets in the human genome using a leukemia cell line K562. We identified 4,596 ASH1 binding sites, 2,502 of which are in the coding region, mostly in a proximity of promoters. Remaining half of the ASH1 binding sites are in the intergenic region. Analysis of histone methyation patterns revealed that a majority of ASH1 bidning sites are closely associated not only with trimethylated H3K36 (H3K36me3) but also with H3K9me3, shedding light for the first time to H3K36/H3K9 double methylation domains. Of note, an H3K9 methyltransferase SETDB1 is enriched in the ASH1 bidning sites, whereas EZH2 but not SUZ12 of the Polycomb Repression Complex 2 (PRC2) is present in bivalent domains. In addition, a small subset of ASH1 targets bear H3K4me3 and colocalize with RNA polymerase II. These select targets are highly enriched for regulators of gene expression, such as CXXC1, WHSC2/NELFA, and a battery of zinc finger proteins, suggesting that ASH1 might acts as a master regulator of gene expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE76145 | GEO | 2016/12/28

SECONDARY ACCESSION(S): PRJNA306482

REPOSITORIES: GEO

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The Trithorax group protein ASH1 requires a combination of BAH domain and AT hooks, but not the SET domain, for mitotic chromatin binding and survival

Project description:The Drosophila Trithorax group (TrxG) protein ASH1 remains associated with mitotic chromatin through mechanisms that are poorly understood. ASH1 dimethylates histone H3 at lysine 36 via its SET domain. Here we identify domains of the TrxG protein ASH1 that are required for mitotic chromatin attachment in living Drosophila. Quantitative live imaging demonstrates that ASH1 requires AT hooks and the BAH domain but not the SET domain for full chromatin binding in metaphase, and that none of these domains are essential for interphase binding. Genetic experiments show that disruptions of the AT hooks and the BAH domain together, but not deletion of the SET domain alone, are lethal. Transcriptional profiling demonstrates that intact ASH1 AT hooks and the BAH domain are required to maintain expression levels of a specific set of genes, including several involved in cell identity and survival. This study identifies in vivo roles for specific ASH1 domains in mitotic binding, gene regulation and survival that are distinct from its functions as a histone methyltransferase.

2021-07-31 | GSE95226 | GEO

Mrg15 allosterically activates Ash1’s H3K36 methyltransferase activity and facilitates Ash1’s trithorax group protein function in Drosophila

Project description:Ash1 is a classic Trithorax group protein possessing an H3K36-specific histone methyltransferase activity. Ash1 plays a critical role in antagonizing Polycomb silencing and its loss-of-function mutations lead to inactivation of certain Hox genes and homeotic transformation. Here, we report the purification of Ash1 complex with the identification of two novel subunits, Mrg15 and Nurf55. Interestingly, Mrg15 stimulates the enzymatic activity of Ash1 in vitro, and such stimulation is independent of the chromo domain of Mrg15. In vivo, Mrg15 is recruited by Ash1 to their common target genes and Mrg15 is essential for the proper deposition of H3K36me2 at these regions.

2017-10-04 | GSE93100 | GEO

Analysis of the trithorax Group (trxG) genes ash2 and ash1 wing imaginal disc transcriptomes.

Project description:The absent, small or homeotic discs 2 (ash2) gene, a member of the trithorax Group (trxG) of transcriptional regulators, is functionally related to ash1. However, ASH2 and ASH1 belong to distinct multimeric complexes of unknown composition and it is unclear how they act to regulate transcription. In this study, examination of gene expression profiles in wing imaginal discs from ash2 and ash1 mutants revealed their transcriptomes are very similar and correlate with wing phenotypes. Keywords: loss of function analysis

2007-07-31 | GSE4923 | GEO

Regulation and function of H3K36 di-methylation by the trithorax-group protein complex AMC

Project description:The goal of this study was to identify genes that are differentially expressed in animals that lack the histone methyltransferase Ash1 that generates H3K36 di-methylation

2018-03-28 | GSE108120 | GEO

ASH1 Q4177.S2

Project description:modENCODE_submission_2984 This submission comes from a modENCODE project of Gary Karpen. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We aim to determine the locations of 125 chromosomal proteins across For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-chip. BIOLOGICAL SOURCE: Cell Line: S2-DRSC; Tissue: embryo-derived cell-line; Developmental Stage: late embryonic stage; Sex: Male; NUMBER OF REPLICATES: 4; EXPERIMENTAL FACTORS: Cell Line S2-DRSC; Antibody ASH1 Q4177 (target is ASH1)

2010-11-18 | E-GEOD-25361 | biostudies-arrayexpress

Ash1 and Tup1 Dependent Repression of the Saccharomyces cerevisiae HO promoter Requires Activator-Dependent Nucleosome Eviction

Project description:Transcriptional regulation of the Saccharomyces cerevisiae HO gene is highly complex, requiring a balance of multiple activating and repressing factors to ensure that only a few transcripts are produced in mother cells within a narrow window of the cell cycle. Here, we show that the Ash1 repressor associates with two DNA sequences that are usually concealed within nucleosomes in the HO promoter and recruits the Tup1 corepressor and the Rpd3 histone deacetylase, both of which are required for full repression in daughters. Genome-wide ChIP identified greater than 200 additional sites of co-localization of these factors, primarily within large, intergenic regions from which they could regulate adjacent genes. Most Ash1 binding sites are in nucleosome depleted regions (NDRs), while a small number overlap nucleosomes, similar to HO. We demonstrate that Ash1 binding to the HO promoter does not occur in the absence of the Swi5 transcription factor, which recruits coactivators that evict nucleosomes, including the nucleosomes obscuring the Ash1 binding sites. In the absence of Swi5, artificial nucleosome depletion allowed Ash1 to bind, demonstrating that nucleosomes are inhibitory to Ash1 binding. The location of binding sites within nucleosomes may therefore be a mechanism for limiting repressive activity to periods of nucleosome eviction that are otherwise associated with activation of the promoter. Our results illustrate that activation and repression can be intricately connected, and events set in motion by an activator may also ensure the appropriate level of repression and reset the promoter for the next activation cycle.

2020-12-01 | GSE158180 | GEO

Ash1 ChIP-chip data from murine Embyonic Stem cells

Project description:Ash1 is a Trithorax Group (TrxG) protein with histone methyl transferase activity that is associated with gene activation. Here we use ChIP-chip to determine the occupancy of Ash1 at promoters in murine embryonic stem cells. This dataset includes singlet ChIP-chip data targeting Ash1 in murine Embryonic stem cells.

2010-05-14 | E-GEOD-20063 | biostudies-arrayexpress

Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila.

Project description: Not available

| S-EPMC5696344 | biostudies-literature

Ash1 ChIP-chip data from murine Embyonic Stem cells

2010-02-28 | GSE20063 | GEO

Chromatin maps of the Drosophila melanogaster TrxG protein Ash1 and FSH

Project description:Trithorax group (TrxG) proteins counteract Polycomb silencing by an as yet uncharacterized mechanism. A well-known member of the TrxG is the histone methyltransferase Absent, Small, or Homeotic discs 1 (ASH1). In Drosophila ASH1 is needed for the maintenance of Hox gene expression throughout development, which is tightly coupled to preservation of cell identity. In order to understand the molecular function of ASH1 in this process, we performed affinity purification of tandem-tagged ASH1 followed by mass spectrometry (AP-MS) and identified FSH, another member of the TrxG as interaction partner. Here we provide genome-wide chromatin maps of both proteins based on ChIP-seq. Our Dataset comprises of 4 ChIP-seq samples using chromatin from S2 cells which was immunoprecipitated, using antibodies against Ash1, FSH-L and FSH-SL.

2013-06-30 | E-GEOD-30820 | biostudies-arrayexpress

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