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Two enhancers synergistically regulate HoxB genes expressions and retinoic acid-induced early ESCs differentiation through 3D chromatin structure

ABSTRACT: Two enhancers synergistically regulate HoxB genes expressions and retinoic acid-induced early ESCs differentiation through 3D chromatin structure

PROVIDER: PRJNA695544 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13572970_1.fastq.gz	Fastqsanger.gz
	SRR13572970_2.fastq.gz	Fastqsanger.gz
	SRR13572971_1.fastq.gz	Fastqsanger.gz
	SRR13572971_2.fastq.gz	Fastqsanger.gz
	SRR13572972_1.fastq.gz	Fastqsanger.gz

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Two enhancers synergistically regulate HoxB genes expressions and retinoic acid-induced early ESCs differentiation through 3D chromatin structure

Project description:Homeobox B cluster (HoxB) genes play important roles in RA-induced early ESCs differentiation. In this study, we identified two enhancers synergistically regulate HoxB genes expressions through 3D chromatin structure and thus regulate RA-induced early ESCs differentiation. 4C data showed interactions between HoxB genes and the two enhancers. CRISPR/Cas9-mediated individual or compound deletion of the two enhancers significantly inhibits HoxB genes expressions while transcriptome analysis revealed that RA induced early ESCs differentiation was blocked in the enhancer KO cells. Our study suggests new mechanism by which two enhancers regulate HoxB genes expressions and retinoic acid-induced early ESCs differentiation through 3D chromatin structure.

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Project description:The mechanism for sex determination in mammalian germ cells remains unclear. Here, we reconstitute the female sex determination in mouse germ cells in vitro under a defined condition without the use of gonadal somatic cells. We show that retinoic acid (RA) and its key effector, STRA8, are not sufficient to induce the female germ-cell fate. In contrast, bone morphogenetic protein (BMP) and RA synergistically induce primordial germ cells (PGCs)/PGC-like cells (PGCLCs) derived from embryonic stem cells (ESCs) into fetal primary oocytes. The induction is characterized by the entry into the meiotic prophase, occurs synchronously and recapitulates cytological and transcriptome progression in vivo faithfully. Importantly, the female germ-cell induction necessitates a proper cellular competence–most typically, DNA demethylation of relevant genes–which is observed in appropriately propagated PGCs/PGCLCs, but not in PGCs/PGCLCs immediately after induction. This provides an explanation for the differential function of BMP signaling between PGC specification and female germ-cell induction. Ou findings represent a framework for a comprehensive delineation of the sex-determination pathway in mammalian germ cells, including humans.

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