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

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

PROVIDER: PRJNA592985 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10574200.fastq.gz	Fastqsanger.gz
	SRR10574201.fastq.gz	Fastqsanger.gz
	SRR10574202.fastq.gz	Fastqsanger.gz
	SRR10574203.fastq.gz	Fastqsanger.gz
	SRR10574204.fastq.gz	Fastqsanger.gz

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

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

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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]

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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

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

2020-12-14 | GSE141272 | GEO

Genome-wide H2A.X deposition in mouse ESC orchestrated by environmental cue-induced demethylation

Project description:Epigenetic landscape in pluripotent stem cells undergoes dynamically changes in response to environmental cues. For example, recent studies suggest that long-term culture of mouse embryonic stem cells (ESCs) in the presence of Mek1/2 and Gsk3β inhibitors (2i culture) leads to the irreversible loss of 5mC and its oxidative derivatives (5hmC, 5fC, and 5caC) as well as genomic redistribution of the histone variant H2A.X, which underlie the impaired developmental potential. However, it remains unclear whether such epigenetic changes are mechanistically connected or merely coincidental. In this study, we demonstrate that the accumulation of oxidative derivatives of 5mC, i.e. 5fC/5caC, serve as potent upstream signals for recruiting H2A.X in ESCs. Furthermore, our data suggest that global H2A.X redistribution in 2i cultured ESCs is due to the loss of 5fc/5caC. We show that the 2i condition also diminishes a recently discovered DNA modification, N6-mA. Moreover, we find that alternative culture conditions, which maintain normal developmental potential, can preserve 5mC and its derivatives, N6-mA and H2A.X deposition in ESCs. Taken together, our results revealed that rare DNA epigenetic modifications and histone variant serve as genome sensors for environmental cues in ESCs and early development.

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