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TET1 non-catalytic activity shapes the chromatin-landscape that directs de novo methylation establishment in the male germline

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE318256 | GEO | 2026/07/22

REPOSITORIES: GEO

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TET1 non-catalytic activity shapes the chromatin-landscape that directs de novo methylation establishment in the male germline [5hmCSeal]

Project description: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 Tet1HxD mouse line, we demonstrate a non-catalytic role of TET1 in promoting H3K4me3 deposition and protecting a subset of sperm hypomethylated regions from aberrant methylation in prospermatogonia.

2026-07-22 | GSE318255 | GEO

TET1 non-catalytic activity shapes the chromatin-landscape that directs de novo methylation establishment in the male germline [RNAseq]

2026-07-22 | GSE318254 | GEO

TET1 non-catalytic activity shapes the chromatin-landscape that directs de novo methylation establishment in the male germline [CUTandRUN]

2026-07-22 | GSE318253 | GEO

TET1 non-catalytic activity shapes the chromatin landscape that directs de novo methylation establishment in the male germline [methylation array]

2026-07-22 | GSE319129 | GEO

TET1 non-catalytic activity shapes the chromatin-landscape that directs de novo methylation establishment in the male germline

Project description:TET1 non-catalytic activity shapes the chromatin-landscape that directs de novo methylation establishment in the male germline

| PRJNA1416980 | ENA

TET1 non-catalytic activity shapes the chromatin-landscape that directs de novo methylation establishment in the male germline [CUTandRUN]

Project description:TET1 non-catalytic activity shapes the chromatin-landscape that directs de novo methylation establishment in the male germline [CUTandRUN]

| PRJNA1416984 | ENA

TET1 non-catalytic activity shapes the chromatin-landscape that directs de novo methylation establishment in the male germline [5hmCSeal]

Project description:TET1 non-catalytic activity shapes the chromatin-landscape that directs de novo methylation establishment in the male germline [5hmCSeal]

| PRJNA1416982 | ENA

TET1 non-catalytic activity shapes the chromatin-landscape that directs de novo methylation establishment in the male germline [RNAseq]

Project description:TET1 non-catalytic activity shapes the chromatin-landscape that directs de novo methylation establishment in the male germline [RNAseq]

| PRJNA1416987 | ENA

TET1 non-catalytic activity shapes the chromatin landscape that directs de novo methylation establishment in the male germline [methylation array]

Project description:TET1 non-catalytic activity shapes the chromatin landscape that directs de novo methylation establishment in the male germline [methylation array]

| PRJNA1422153 | ENA

NSD1-deposited H3K36me2 directs de novo methylation in the mouse male germline and counteracts Polycomb-associated silencing

Project description:While de novo DNA methylation (DNAme) in mammalian germ cells is dependent upon DNMT3A and DNMT3L, oocytes and spermatozoa show distinct patterns of DNAme. In mouse oocytes, de novo DNAme requires the lysine methyltransferase (KMTase) SETD2, which deposits H3K36me3. Surprisingly, we show here that SETD2 is dispensable for de novo DNAme in the male germline. Rather, the KMTase NSD1, which broadly deposits H3K36me2 in euchromatic regions, plays a critical role in de novo DNAme in prospermatogonia, including of imprinted genes. However, males deficient in germline NSD1 show a more severe defect in spermatogenesis than Dnmt3l-/- males. Furthermore, unlike DNMT3L, NSD1 safeguards a subset of genes against H3K27me3-associated transcriptional silencing. In contrast, H3K36me2 plays only a minor role in de novo DNAme during oogenesis and females with NSD1 deficient oocytes are fertile. Thus, the sexually dimorphic pattern of DNAme in mature mouse gametes is driven by distinct profiles of H3K36 methylation.

2020-07-10 | GSE148150 | GEO

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