{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Prasasya RD"],"funding":["NICHD NIH HHS","NIEHS NIH HHS","NHGRI","NICHD","NHGRI NIH HHS","NIGMS NIH HHS","NIGMS"],"pagination":["1010-1027.e8"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11042979"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["59(8)"],"pubmed_abstract":["Ten-eleven translocation (TET) enzymes iteratively oxidize 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine to facilitate active genome demethylation. Whether these bases are required to promote replication-coupled dilution or activate base excision repair during mammalian germline reprogramming remains unresolved due to the inability to decouple TET activities. Here, we generated two mouse lines expressing catalytically inactive TET1 (Tet1-HxD) and TET1 that stalls oxidation at 5hmC (Tet1-V). Tet1 knockout and catalytic mutant primordial germ cells (PGCs) fail to erase methylation at select imprinting control regions and promoters of meiosis-associated genes, validating the requirement for the iterative oxidation of 5mC for complete germline reprogramming. TET1<sup>V</sup> and TET1<sup>HxD</sup> rescue most hypermethylation of Tet1<sup>-/-</sup> sperm, suggesting the role of TET1 beyond its oxidative capability. We additionally identify a broader class of hypermethylated regions in Tet1 mutant mouse sperm that depend on TET oxidation for reprogramming. Our study demonstrates the link between TET1-mediated germline reprogramming and sperm methylome patterning."],"journal":["Developmental cell"],"pubmed_title":["Iterative oxidation by TET1 is required for reprogramming of imprinting control regions and patterning of mouse sperm hypomethylated regions."],"pmcid":["PMC11042979"],"funding_grant_id":["R01 HG010646","K99 HD112543","R01 GM118501","P30 ES013508","R01 GM146388","R01 GM051279","F32 HD101230","F31 HD098764"],"pubmed_authors":["Liu Z","Leu NA","Bartolomei MS","Prasasya RD","Fowler JM","Laird DJ","Wu S","Cincotta SA","Caldwell BA","Kohli RM"],"additional_accession":[]},"is_claimable":false,"name":"Iterative oxidation by TET1 is required for reprogramming of imprinting control regions and patterning of mouse sperm hypomethylated regions.","description":"Ten-eleven translocation (TET) enzymes iteratively oxidize 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine to facilitate active genome demethylation. Whether these bases are required to promote replication-coupled dilution or activate base excision repair during mammalian germline reprogramming remains unresolved due to the inability to decouple TET activities. Here, we generated two mouse lines expressing catalytically inactive TET1 (Tet1-HxD) and TET1 that stalls oxidation at 5hmC (Tet1-V). Tet1 knockout and catalytic mutant primordial germ cells (PGCs) fail to erase methylation at select imprinting control regions and promoters of meiosis-associated genes, validating the requirement for the iterative oxidation of 5mC for complete germline reprogramming. TET1<sup>V</sup> and TET1<sup>HxD</sup> rescue most hypermethylation of Tet1<sup>-/-</sup> sperm, suggesting the role of TET1 beyond its oxidative capability. We additionally identify a broader class of hypermethylated regions in Tet1 mutant mouse sperm that depend on TET oxidation for reprogramming. Our study demonstrates the link between TET1-mediated germline reprogramming and sperm methylome patterning.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-06-01T05:18:52.494Z","creation":"2026-04-08T09:23:51.928Z"},"accession":"S-EPMC11042979","cross_references":{"pubmed":["38569549"],"doi":["10.1016/j.devcel.2024.02.012"]}}