TET1 noncatalytic activity shapes the chromatin landscape associated with de novo methylation establishment in the male germline.

Authors

Rexxi D Prasasya, Jean J Kim, Zhengfeng Liu, Rahul M Kohli, Marisa S Bartolomei

Published in

Genes & development. Jul 14, 2026. Epub Jul 14, 2026.

Abstract

In the germline, DNA methylation is globally erased in primordial germ cells (PGCs), enabling establishment of sex-specific methylomes in prospermatogonia or oocytes. The catalytic activity of TET1 is required for complete demethylation in PGCs, yet sperm from Tet1 ^-/- mice display methylation defects not explained by incomplete erasure. Instead, these defects arise from abnormal de novo methylation during development, coinciding with erosion of H3K4me3, a chromatin modification that blocks DNMT3A/3L. Using a catalytically inactive Tet1 ^HxD mouse line, we demonstrate a noncatalytic role of TET1 in promoting H3K4me3 deposition and protecting a subset of sperm hypomethylated regions from aberrant methylation in prospermatogonia.

PMID:
42448565
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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