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YTHDF1 facilitates PRC1 mediated H2AK119ub in Human ES Cells

ABSTRACT: YTHDF1 facilitates PRC1 mediated H2AK119ub in Human ES Cells

PROVIDER: PRJNA842403 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19403692_1.fastq.gz	Fastqsanger.gz
	SRR19403692_2.fastq.gz	Fastqsanger.gz
	SRR19403693_1.fastq.gz	Fastqsanger.gz
	SRR19403693_2.fastq.gz	Fastqsanger.gz
	SRR19403694_1.fastq.gz	Fastqsanger.gz

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YTHDF1 facilitates PRC1 mediated H2AK119ub in Human ES Cells

Project description:YTHDF1 facilitates PRC1 mediated H2AK119ub in Human ES Cells

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YTHDF1 facilitates PRC1 mediated H2AK119ub in Human ES Cells

Project description:Polycomb repressive complexes( PRCs) play critical role in cell fate decisions during normal development as well as disease progression through mediate histone modifications such as H3K27me3 and H2AK119ub. How exactly PRCs recruited to chromatin remains to be fully illuminated. Here, we report that YTHDF1, a N6-methyladenine (m6A) RNA reader previously known being mainly cytoplasmic, associates with RNF2, a PRC1 protein that mediates H2AK119ub in human embryonic stem cells (hESCs). Specifically, a portion of YTHDF1 localizes in the nuclei and associates with RNF2/ H2AK119ub on a subset of gene loci related to neural development functions. Knock-down YTHDF1 attenuates H2AK119ub modification on these genes and promotes neural differentiation in hESCs. Our findings provide another non-canonical mechanism of YTHDF1 to participate in PRC1 mediated chromatin modification in hESCs.

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Elucidation of BMI1, RYBP and H2AK119ub interactomes in Glioblastoma

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Functional dissection of PRC1 subunits RYBP and YAF2 during neural differentiation of embryonic stem cells

Project description:Polycomb repressive complex 1 (PRC1) comprises two different complexes: CBX-containing canonical PRC1 (cPRC1) and RYBP/YAF2-containing variant PRC1 (vPRC1). RYBP and its paralog YAF2 recruit vPRC1 to catalyze H2AK119ub through a positive-feedback model. Here, we show that expression of RYBP and YAF2 decreases and increases, respectively, during neural differentiation of embryonic stem cells (ESCs). Rybp knockout impairs neural differentiation by activating Wnt signaling and derepressing nonneuroectoderm-associated genes. However, Yaf2 knockout promotes neural differentiation and leads to redistribution of RYBP binding, increases enrichment of RYBP and H2AK119ub on the RYBP-YAF2 co-targeted genes, and prevents ectopic derepression of nonneuroectoderm-associated genes in neural-differentiated cells. Furthermore, the phase separations mediated by RYBP alone or together with RING1B are easier and more stable than those by YAF2, which might facilitate the deposition of H2AK119ub more abundantly by RYBP-PRC1 than YAF2-PRC1. Together, this study reveals that RYBP might maintain repressed chromatin more strongly and function differentially in regulating mESC neural differentiation compared with YAF2.

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