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| Status |
Public on Mar 18, 2024 |
| Title |
Combinational effect of the ADD domains of DNMT3A and DNMT3L on DNA methylation landscapes in mouse germ cells [WGBS] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
WGBS (PBAT) and mRNA-seq experiments in oocytes, sperms, and embryoes derived from DNMT3A/DNMT3L-ADD domain mutated mouse.
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| Contributor(s) |
Kubo N, Sasaki H |
| Citation(s) |
38627502 |
| |
| Submission date |
Jul 25, 2023 |
| Last update date |
May 01, 2024 |
| Contact name |
Naoki Kubo |
| E-mail(s) |
naoki.kubo@bioreg.kyushu-u.ac.jp
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| Organization name |
Kyushu University
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| Street address |
3-1-1 Maidashi, Higashi-ku
|
| City |
Fukuoka |
| State/province |
Fukuoka |
| ZIP/Postal code |
812-8582 |
| Country |
Japan |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (13)
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| This SubSeries is part of SuperSeries: |
| GSE238228 |
Combinational effect of the ADD domains of DNMT3A and DNMT3L on DNA methylation landscapes in mouse germ cells |
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| Relations |
| BioProject |
PRJNA998394 |
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