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HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation

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

ORGANISM(S): Mus musculus

PROVIDER: GSE141272 | GEO | 2020/12/14

REPOSITORIES: GEO

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HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation [RNA-Seq]

Project description:During transcriptional activation, chromatin undergoes structural changes with the help of various proteins such as chromatin remodeling factors and histone modifiers in order to make the DNA accessible for the transcription factors and RNA polymerase. We combined ChIP-, MNase- and RNA-sequencing analyzing the Hmga2 knock-out mice and found that HMGA2 is required for promoter specific deposition of the histone variant H2A.X. Consequently, the promoter specific H2A.X deposition resulted in an accumulation of active RNA Polymerase II at these promoters. Stimulation with TGFB1 resulted in increased accumulation of pH2A.X and expression of those “primed” target genes, whereas cells expressing no Hmga2 where not able to respond.

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HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation [Mnase-Seq]

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HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation [ChIP-Seq]

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HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation [TGFB1-ChIP-seq]

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HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation

Project description:HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation

| PRJNA592980 | ENA

HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation [RNA-Seq]

Project description:HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation [RNA-Seq]

| PRJNA592986 | ENA

HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation [Mnase-Seq]

Project description:HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation [Mnase-Seq]

| PRJNA592987 | ENA

HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation [ChIP-Seq]

Project description:HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation [ChIP-Seq]

| PRJNA592988 | ENA

HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation [TGFB1-ChIP-seq]

Project description:HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation [TGFB1-ChIP-seq]

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TET2 catalyzes active DNA demethylation of the Sry promoter and enhances its expression.

Project description:SRY is the master regulator of male sex determination in eutherian mammals. In mice, Sry expression is transcriptionally and epigenetically controlled in a developmental stage-specific manner. The Sry promoter undergoes demethylation in embryonic gonadal somatic cells at the sex-determining period. However, its molecular mechanism and in vivo significance remain unclear. Here, we report that the Sry promoter is actively demethylated during gonadal development, and TET2 plays a fundamental role in Sry demethylation. Tet2-deficient mice showed absence of 5-hydroxymethylcytosine in the Sry promoter. Furthermore, Tet2 deficiency diminished Sry expression, indicating that TET2-mediated DNA demethylation regulates Sry expression positively. We previously showed that the deficiency of the H3K9 demethylase Jmjd1a compromises Sry expression and induces male-to-female sex reversal. Tet2 deficiency enhanced the sex reversal phenotype of Jmjd1a-deficient mice. Thus, TET2-mediated active DNA demethylation and JMJD1A-mediated H3K9 demethylation contribute synergistically to sex determination.

| S-EPMC6748950 | biostudies-literature

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