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Combinational effect of the ADD domains of DNMT3A and DNMT3L on DNA methylation landscapes in mouse germ cells [WGBS]

ABSTRACT: DNA methyltransferase 3A (DNMT3A) and DNA methyltransferase 3-Like (DNMT3L) form functional heterotetramers and ATRX-DNMT3-DNMT3L (ADD) domains, shared by both DNMT3A and DNMT3L, recognizes histone H3 tail unmethylated at lysine-4 (H3K4me0) to deposit DNA methylation properly in mammalian germ cells. However, the combinational and differential role of ADD domains of DNMT3A and DNMT3L in vivo has not been fully defined. Here we analyze both female and male germ cells derived from mouse with amino-acid substitutions in ADD domains of DNMT3A and/or DNMT3L that impair their domain function. Loss of either DNMT3A-ADD or DNMT3L-ADD domain function shows moderate reduction of global CG methylation level, but in different degree, in both germ cells. However, when both DNMT3A and DNMT3L lost their ADD domain functions, reduction of the global CG methylation level is much more severe and comparable with that of Dnmt3a/3L knockout germ cells. In contrast, such double mutant germ cells have thousands of genomic regions where non-CG methylation is aberrantly accumulated. These results highlight a critical role of the combinational function of ADD domains for the robust CG and non-CG methylation in germ cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE238227 | GEO | 2024/03/18

REPOSITORIES: GEO

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Combinational effect of the ADD domains of DNMT3A and DNMT3L on DNA methylation landscapes in mouse germ cells [RNA-seq]

Project description:DNA methyltransferase 3A (DNMT3A) and DNA methyltransferase 3-Like (DNMT3L) form functional heterotetramers and ATRX-DNMT3-DNMT3L (ADD) domains, shared by both DNMT3A and DNMT3L, recognizes histone H3 tail unmethylated at lysine-4 (H3K4me0) to deposit DNA methylation properly in mammalian germ cells. However, the combinational and differential role of ADD domains of DNMT3A and DNMT3L in vivo has not been fully defined. Here we analyze both female and male germ cells derived from mouse with amino-acid substitutions in ADD domains of DNMT3A and/or DNMT3L that impair their domain function. Loss of either DNMT3A-ADD or DNMT3L-ADD domain function shows moderate reduction of global CG methylation level, but in different degree, in both germ cells. However, when both DNMT3A and DNMT3L lost their ADD domain functions, reduction of the global CG methylation level is much more severe and comparable with that of Dnmt3a/3L knockout germ cells. In contrast, such double mutant germ cells have thousands of genomic regions where non-CG methylation is aberrantly accumulated. These results highlight a critical role of the combinational function of ADD domains for the robust CG and non-CG methylation in germ cells.

2024-03-18 | GSE238226 | GEO

Dnmt3L-dependent regulation of DNA methylation promotes stem cells differentiation toward primitive germinal cells [MeDIP-seq]

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Ectopic expression of DNA methyltransferases DNMT3A2 and DNMT3L leads to aberrant hypermethylation and postnatal lethality in mice

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Dnmt3L-dependent regulation of DNA methylation promotes stem cells differentiation toward primitive germinal cells [ChIP-seq]

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2013-09-27 | E-GEOD-49178 | biostudies-arrayexpress

DNA methylation changes in Dnmt3L-deficient mouse embryonic stem cells (mESCs)

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2018-10-04 | GSE116489 | GEO

Dnmt3L-dependent regulation of DNA methylation promotes stem cells differentiation toward primitive germinal cells [Expression array]

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2013-09-27 | E-GEOD-44643 | biostudies-arrayexpress

Dnmt3L-dependent regulation of DNA methylation promotes stem cells differentiation toward primitive germinal cells [ChIP-seq]

Project description:The de novo DNA methyltransferase 3-like (Dnmt3L) is a catalytically inactive DNA methylase that has been previously shown to cooperate with Dnmt3a and Dnmt3b to methylate DNA. Dnmt3L is highly expressed in mouse embryonic stem cells (ESC) but its function in these cells is unknown. We here report that Dnmt3L is required for the differentiation of ESC into primordial germ cells (PGC) through activation of the homeotic gene Rhox5. By genome-wide analysis we found that Dnmt3L is a positive regulator of methylation at gene bodies of housekeeping genes and a negative regulator of methylation at promoters of bivalent genes. We demonstrate that Dnmt3L interacts with the Polycomb PRC2 complex in competition with the DNA methyltransferases Dnmt3a and Dnmt3b to maintain low the methylation level at H3H27me3 regions. Thus, in ESC, Dnmt3L counteracts the activity of de novo DNA methylases to keep low the level of DNA methylation at developmental gene promoters.

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Dnmt3L-dependent regulation of DNA methylation promotes stem cells differentiation toward primitive germinal cells [Expression array]

2013-09-27 | GSE44643 | GEO

Dnmt3L-dependent regulation of DNA methylation promotes stem cells differentiation toward primitive germinal cells [MeDIP-seq]

2013-09-27 | GSE44642 | GEO

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