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PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation [srHC-seq]

ABSTRACT: PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation [srHC-seq]

PROVIDER: PRJNA488480 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7767850.fastq.gz	Fastqsanger.gz
	SRR7767860.fastq.gz	Fastqsanger.gz
	SRR7767870.fastq.gz	Fastqsanger.gz
	SRR7767851.fastq.gz	Fastqsanger.gz
	SRR7767861.fastq.gz	Fastqsanger.gz

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PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation

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PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation [srHC-seq]

Project description:The inability to derive fully functional cell types, such as hepatocytes, from stem cells may emanate from the lack of knowledge about mechanisms that underlie postnatal cell maturation. We characterized hepatic maturation during the postnatal day 14 (P14) to 2-month-old (M2) transition and found more than 3000 genes differentially expressed. Nearly half of such maturation genes have H3K27me3 at their promoters or gene bodies at P14 or M2. Genetic ablation of both PRC2 histone methyltransferases in perinatal livers causes hepatocytes to prematurely differentiate, expressing genes at P14 that would normally be induced later, by M2. Using srHC-seq, a new method to map sonication-resistant heterochromatin, we found that the H3K27me3+ prematurely upregulated genes have euchromatic promoters at P14. We also observed derepression of many non-hepatic lineage genes with euchromatic promoter H3K27me3-marking. Thus, Polycomb repression is used to restrain expression of late liver maturation genes and lineage inappropriate genes at euchromatic promoters.

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EZH1 in Germ Cells Safeguards the Function of PRC2 during Spermatogenesis

Project description:We previously reported the requirement of Polycomb Repressive Complex 2 (PRC2) for spermatogenesis through transcriptional repression of somatic genes and meiosis-specific genes. To characterize how PRC2's two methyltransferase subunits, EZH1 and EZH2, regulate histone H3 lysine 27 (H3K27) methylation during germ cell development, we generated mouse models with a germline ablation of EZH1 and/or EHZ2. Only the combined loss of EZH1 and EZH2 caused a depletion of global H3K27me3 marks and meiotic arrest in spermatocytes. Genome-wide analysis of H3K27me3 in spermatogenic cells revealed that a noncanonical EZH1-PRC2 could establish and maintain this histone mark on somatic genes and certain meiotic genes. Consistent with it having active enhancers in testis, Ezh1 was not only abundant in highly differentiated spermatocytes but also in actively proliferating progenitor and stem germ cells. Taken together, our findings suggest that the expression level of Ezh1 determines the restoration of H3K27 methylation in the absence of the canonical EZH2-PRC2.

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PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation

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

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