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Insulators recruit histone methyltransferase dMes4 to regulate chromatin of flanking genes

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE57168 | GEO | 2014/04/30

SECONDARY ACCESSION(S): PRJNA245820

REPOSITORIES: GEO

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Insulators recruit histone methyltransferase dMes4 to regulate chromatin of flanking genes

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

2014-04-30 | E-GEOD-57168 | biostudies-arrayexpress

Insulators recruit histone methyltransferase dMes4 to regulate chromatin of flanking genes.

Project description:Chromosomal domains in Drosophila are marked by the insulator-binding proteins (IBPs) dCTCF/Beaf32 and cofactors that participate in regulating long-range interactions. Chromosomal borders are further enriched in specific histone modifications, yet the role of histone modifiers and nucleosome dynamics in this context remains largely unknown. Here, we show that IBP depletion impairs nucleosome dynamics specifically at the promoters and coding sequence of genes flanked by IBP binding sites. Biochemical purification identifies the H3K36 histone methyltransferase NSD/dMes-4 as a novel IBP cofactor, which specifically co-regulates the chromatin accessibility of hundreds of genes flanked by dCTCF/Beaf32. NSD/dMes-4 presets chromatin before the recruitment of transcriptional activators including DREF that triggers Set2/Hypb-dependent H3K36 trimethylation, nucleosome positioning, and RNA splicing. Our results unveil a model for how IBPs regulate nucleosome dynamics and gene expression through NSD/dMes-4, which may regulate H3K27me3 spreading. Our data uncover how IBPs dynamically regulate chromatin organization depending on distinct cofactors.

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Insulators recruit histone methyltransferase dMes4 to regulate chromatin of flanking genes

Project description:Insulators recruit histone methyltransferase dMes4 to regulate chromatin of flanking genes

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SFMBT1 Functions with LSD1 to Regulate Expression of Canonical Histone Genes and Chromatin-Related Factors

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

2013-03-26 | E-GEOD-45489 | biostudies-arrayexpress

Histone methyltransferase Dot1L recruits O-GlcNAc transferase to target chromatin sites to regulate histone O-GlcNAcylation.

Project description:O-GlcNAc transferase (OGT) is the distinctive enzyme responsible for catalyzing O-GlcNAc addition to the serine or threonine residues of thousands of cytoplasmic and nuclear proteins involved in such basic cellular processes as DNA damage repair, RNA splicing, and transcription preinitiation and initiation complex assembly. However, the molecular mechanism by which OGT regulates gene transcription remains elusive. Using proximity labeling-based mass spectrometry, here, we searched for functional partners of OGT and identified interacting protein Dot1L, a conserved and unique histone methyltransferase known to mediate histone H3 Lys79 methylation, which is required for gene transcription, DNA damage repair, cell proliferation, and embryo development. Although this specific interaction with OGT does not regulate the enzymatic activity of Dot1L, we show that it does facilitate OGT-dependent histone O-GlcNAcylation. Moreover, we demonstrate that OGT associates with Dot1L at transcription start sites and that depleting Dot1L decreases OGT associated with chromatin globally. Notably, we also show that downregulation of Dot1L reduces the levels of histone H2B S112 O-GlcNAcylation and histone H2B K120 ubiquitination in vivo, which are associated with gene transcription regulation. Taken together, these results reveal that O-GlcNAcylation of chromatin is dependent on Dot1L.

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Human tRNA genes function as chromatin insulators.

Project description:Insulators help separate active chromatin domains from silenced ones. In yeast, gene promoters act as insulators to block the spread of Sir and HP1 mediated silencing while in metazoans most insulators are multipartite autonomous entities. tDNAs are repetitive sequences dispersed throughout the human genome and we now show that some of these tDNAs can function as insulators in human cells. Using computational methods, we identified putative human tDNA insulators. Using silencer blocking, transgene protection and repressor blocking assays we show that some of these tDNA-containing fragments can function as barrier insulators in human cells. We find that these elements also have the ability to block enhancers from activating RNA pol II transcribed promoters. Characterization of a putative tDNA insulator in human cells reveals that the site possesses chromatin signatures similar to those observed at other better-characterized eukaryotic insulators. Enhanced 4C analysis demonstrates that the tDNA insulator makes long-range chromatin contacts with other tDNAs and ETC sites but not with intervening or flanking RNA pol II transcribed genes.

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Phosphorylated histone variant γH2Av is associated with chromatin insulators in Drosophila.

Project description:Chromatin insulators are responsible for orchestrating long-range interactions between enhancers and promoters throughout the genome and align with the boundaries of Topologically Associating Domains (TADs). Here, we demonstrate an association between gypsy insulator proteins and the phosphorylated histone variant H2Av (γH2Av), normally a marker of DNA double strand breaks. Gypsy insulator components colocalize with γH2Av throughout the genome, in polytene chromosomes and in diploid cells in which Chromatin IP data shows it is enriched at TAD boundaries. Mutation of insulator components su(Hw) and Cp190 results in a significant reduction in γH2Av levels in chromatin and phosphatase inhibition strengthens the association between insulator components and γH2Av and rescues γH2Av localization in insulator mutants. We also show that γH2Av, but not H2Av, is a component of insulator bodies, which are protein condensates that form during osmotic stress. Phosphatase activity is required for insulator body dissolution after stress recovery. Together, our results implicate the H2A variant with a novel mechanism of insulator function and boundary formation.

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SFMBT1 Functions with LSD1 to Regulate Expression of Canonical Histone Genes and Chromatin-Related Factors

Project description:This SuperSeries is composed of the SubSeries listed below.

2013-03-26 | GSE45489 | GEO

The histone methyltransferase MLL3 regulates genome-scale circadian transcription

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

2013-01-01 | E-GEOD-37396 | biostudies-arrayexpress

Histone H3K9 Methyltransferase G9a Represses PPAR? Expression and Adipogenesis

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

2013-02-01 | E-GEOD-41457 | biostudies-arrayexpress