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Regulation of 3D genome organization, transcription and histone H3K9me2 by histone H3K9 methyltransferases [HiC]

ABSTRACT: Regulation of 3D genome organization, transcription and histone H3K9me2 by histone H3K9 methyltransferases [HiC]

PROVIDER: PRJNA715217 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13990218_1.fastq.gz	Fastqsanger.gz
	SRR13990218_2.fastq.gz	Fastqsanger.gz
	SRR13990219_1.fastq.gz	Fastqsanger.gz
	SRR13990219_2.fastq.gz	Fastqsanger.gz
	SRR13990220_1.fastq.gz	Fastqsanger.gz

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Regulation of 3D genome organization, transcription and histone H3K9me2 by histone H3K9 methyltransferases [HiC]

Project description:Histone H3 lysine 9 dimethylation (H3K9me2) is a highly conserved silencing epigenetic mark. Chromatin marked with H3K9me2 forms large domains in mammalian cells and overlaps well with lamina-associated domains and the B compartment defined by Hi-C. However, the role of H3K9me2 in 3-dimensional (3D) genome organization remains unclear. We investigated genome-wide H3K9me2 distribution, transcriptome, and 3D genome organization in mouse embryonic stem cells following the inhibition or depletion of five H3K9 methyltransferases (MTases): G9a, GLP, SETDB1, SUV39H1, and SUV39H2. H3K9me2 was regulated by all five MTases; however, H3K9me2 and transcription in the A and B compartments were regulated by different MTases. H3K9me2 in A compartments was primarily regulated by G9a/GLP and SETDB1, while H3K9me2 in the B compartments was regulated by all five MTases. Furthermore, decreased H3K9me2 correlated with changes to the more active compartmental state that accompanied transcriptional activation.

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Project description:Heterochromatin is a key architectural feature of eukaryotic chromosomes, which is critical for cell type specific gene expression and genome stability. In the mammalian nucleus, heterochromatin is segregated from transcriptionally active genomic regions, and exists as large condensed and inactive nuclear compartment. However, the underlying mechanism of spatial organization of heterochromatin is still poorly understood. Histone H3 lysine 9 di- and tri-methylation (H3K9me2/3) and lysine 27 trimethylation (H3K27me3) are two major epigenetic modifications that define constitutive and facultative heterochromatin, respectively. In mammals, there are at least five H3K9 methyltransferases (SUV39H1, SUV39H2, SETDB1, G9a and GLP) and two H3K27 methyltransferases (EZH1 and EZH2). In this study, we addressed the role of H3K9 and H3K27 methylation in heterochromatin organization by using a combination of compound mutant cells for the five H3K9 methyltransferases and an EZH1/2 dual inhibitor, DS3201. We show that H3K27me3, which is normally segregated from H3K9me2/3, was redistributed to regions targeted by H3K9me2/3 after the loss of H3K9 methylation, and loss of both H3K9 and H3K27 methylation resulted in impaired both condensation and spatial organization of heterochromatin. Our data demonstrate that the two major repressive epigenome pathways exclusively but also coordinately maintain H3K9me2/3-marked heterochromatin organization in mammalian cells.

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