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Expression regulation by Yaf2 in mouse embryonic stem cells

ABSTRACT: Expression regulation by Yaf2 in mouse embryonic stem cells

PROVIDER: PRJNA454203 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7081801_1.fastq.gz	Fastqsanger.gz
	SRR7081801_2.fastq.gz	Fastqsanger.gz
	SRR7081802_1.fastq.gz	Fastqsanger.gz
	SRR7081802_2.fastq.gz	Fastqsanger.gz
	SRR7081803_1.fastq.gz	Fastqsanger.gz

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Expression regulation by Yaf2 in mouse embryonic stem cells

Project description:The Polycomb group (PcG) proteins are the key epigenetic regulators with well-established roles in stem cell maintenance. To date, biochemical analyses have identified noncanonical PRC1(nc-PRC1) complexes characterized by the presence of Rybp/Yaf2 and the lack of CBX proteins. The biological significance of these nc-PRC1s and the potential mechanisms by which they mediate gene repression are largely unknown. Here we show that disruption of Yaf2 results in compromised proliferation and abnormal differentiation in mouse embryonic stem cells (mESCs). Deletion analysis identifies the region encompassing amino acid residues 102–150 required for the assembly of Yaf2 into nc-PRC1 complexes. Furthermore, we found that substitution of serine 166 by alanine (S166A) caused a loss of Yaf2-phosphorylation signal in mESCs. Loss of such Yaf2-phosphorylation compromises Ring1B-mediated H2A monoubiquitination and in turn lose its ability to repress target gene expression. We therefore propose that Yaf2 phosphorylation enhances its ability to maintain the pluripotent state in mESCs.

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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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Project description:Polycomb repressive complex 1 (PRC1) comprises two different complexes: CBX-containing canonical PRC1 (cPRC1) and RYBP/YAF2-containing variant PRC1 (vPRC1). RYBP-vPRC1 or YAF2-vPRC1 catalyzes H2AK119ub through a positive-feedback model; however, whether RYBP and YAF2 have different regulatory functions is still unclear. Here, we show that the 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 cotargeted genes, and prevents ectopic derepression of nonneuroectoderm-associated genes in neural-differentiated cells. Taken together, this study reveals that RYBP and YAF2 function differentially in regulating mESC neural differentiation.

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