TET1 facilitates specification of early human lineages including germ cells.

ABSTRACT: Ten Eleven Translocation 1 (TET1) is a regulator of localized DNA demethylation through the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). To examine DNA demethylation in human primordial germ cell-like cells (hPGCLCs) induced from human embryonic stem cells (hESCs), we performed bisulfite-assisted APOBEC coupled epigenetic sequencing (bACEseq) followed by integrated genomics analysis. Our data indicates that 5hmC enriches at hPGCLC-specific NANOG, SOX17 or TFAP2C binding sites on hPGCLC induction, and this is accompanied by localized DNA demethylation. Using CRISPR-Cas9, we show that deleting the catalytic domain of TET1 reduces hPGCLC competency when starting with hESC cultured on mouse embryonic fibroblasts, and this phenotype can be rescued after transitioning

SUBMITTER: Hsu FM 

PROVIDER: S-EPMC10345126 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature