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DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells

ABSTRACT: We analyzed transcriptome profiles of postnatal germ cells and demonstrated that DNMT3L is important for spermatogonial stem/progenitor cell development Examination of wild-type and Dnmt3l knockout smaples in postnatal male germ cells

ORGANISM(S): Mus musculus

SUBMITTER: Shau-Ping Lin

PROVIDER: E-GEOD-54411 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells.

Liao Hung-Fu HF Chen Wendy S C WS Chen Yu-Hsiang YH Kao Tzu-Hao TH Tseng Yen-Tzu YT Lee Chien-Yueh CY Chiu Yu-Chiao YC Lee Pei-Lung PL Lin Qian-Jia QJ Ching Yung-Hao YH Hata Kenichiro K Cheng Winston T K WT Tsai Mong-Hsun MH Sasaki Hiroyuki H Ho Hong-Nerng HN Wu Shinn-Chih SC Huang Yen-Hua YH Yen Pauline P Lin Shau-Ping SP

Development (Cambridge, England) 20140521 12

The ability of adult stem cells to reside in a quiescent state is crucial for preventing premature exhaustion of the stem cell pool. However, the intrinsic epigenetic factors that regulate spermatogonial stem cell quiescence are largely unknown. Here, we investigate in mice how DNA methyltransferase 3-like (DNMT3L), an epigenetic regulator important for interpreting chromatin context and facilitating de novo DNA methylation, sustains the long-term male germ cell pool. We demonstrated that stem c ...[more]

PMID: 24850856

Similar Datasets

DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells

Project description:We analyzed transcriptome profiles of postnatal germ cells and demonstrated that DNMT3L is important for spermatogonial stem/progenitor cell development

2014-07-03 | GSE54411 | GEO

Dnmt3l-knockout donor cells improve somatic cell nuclear transfer reprogramming efficiency

Project description:We found that Dnmt3l-KO donor cells display decreased levels of H3K9me3 and H3K27me3 accumulation, higher level of active histone mark H3K27ac and increased cytoplasmic localization of HDAC1, implicating a permissive epigenetic state beneficial for nuclear reprogramming. To investigate the gene expression profiles of MEFs and to find out the potential genes responsible for the improvement of Dnmt3l-KO cloned embryos.

2015-08-01 | E-GEOD-69007 | biostudies-arrayexpress

Genome-wide analysis of Dnmt3L heterozygous and wildtype spermatocytes and spermatids

Project description:Comparison of gene expression differences between Dnmt3L heterozygous and wildtype pachytene spermatocytes, and similarly between Dnmt3L heterozygous and wildtype round spermatids which were isolated from the Dnmt3L knockout mouse line. This array was conducted to address the hypothesis that Dnmt3L heterozygosity results in deregulated gene expression within spermatocytes and spermatids. Results show that Dnmt3L heterozygosity causes numerous genes to be differentially regulated on a genome-wide level, showing that DNMT3L has an important role in regulating gene expression within these male germ cells.

2011-03-01 | GSE20241 | GEO

Genome-wide analysis of Dnmt3L heterozygous and wildtype spermatocytes and spermatids

2011-03-01 | E-GEOD-20241 | biostudies-arrayexpress

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

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 | GSE238227 | GEO

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

2024-03-18 | GSE238226 | GEO

Dnmt3L-dependent regulation of DNA methylation promotes stem cells differentiation toward primitive germinal cells [MeDIP-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 methyl transferases 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. Examination of 5mC in shGFP and shDnmt3L ESC by MeDIP-Seq

2013-09-27 | E-GEOD-44642 | 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. Examination of Ezh2 ChIP-Seq in shGFP and shDnmt3L ESC. Examination of Dnmt3L ChIP-Seq in shGFP and shSuz12 ESC.

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

Dnmt3L-histone H3 binding is necessary for male fertility and non-CG methylation

Project description:Patterns of DNA methylation are established during gametogenesis. The catalytically-inactive adaptor Dnmt3L is crucial to ensure this occurs correctly. In vitro, Dnmt3L binds to the N terminal tail of histone H3 but the function of this interaction during development is unknown. Here we show that Dnmt3L-histone H3 interaction is necessary for spermatogenesis. Mutant animals exhibit reduced fertility, defective methylation establishment at retrotransposons coupled with their reactivation and meiotic catastrophe. The spermatogonial stem cell pool is also defective, with mutant cells displaying marked changes in gene expression. Genome-wide methylation analysis reveals reductions in CG methylation as well as severe loss of non-CG methylation suggesting that non-CG methylation is specifically sensitive to the ability of Dnmt3L to bind histone H3. MethylC-Seq of wild-type and Dnmt3LA/A 1dpp prospermatagonia

2015-01-14 | E-GEOD-58066 | biostudies-arrayexpress

DNMT3L is crucial for the osteogenesis ability of mesenchymal stem cells

Project description:DNA methyltransferase 3-like (DNMT3L), an epigenetic modulating factor known to participate in facilitating de novo DNA methylation with DNMT3A and DNMT3B, is mainly expressed in pluripotent stem cells and germ cells. We observed that Dnmt3l deficiency imped mesenchymal stem cells (MSCs) self-renewal and proliferation by colony forming unit – fibroblast (CFU-F) assay and growth curve test. Furthermore, calcium precipitation is dramatically decreased after 14 days of osteogenic induction in Dnmt3l KO mice derived MSCs. We further investigated the gene expression pattern in undifferentiated and day 3 of osteogenic induction MSCs derived from wild type and Dnmt3l KO mice respectively by RNA-sequencing, and found that differentially expressed genes (DEGs) before osteogenesis are highlighted in various pathways related to bone and the DEGs from day 3 of osteogenic induction MSCs are associated with proliferation and differentiation. Collectively, these results indicate that Dnmt3l deficiency abrogated MSCs property and may play role in MSC differentiation potential. By these results, we suggested that transiently expressed DNMT3L in pluripotent stem cells contribute to mediation of epigenetic mark establishment and have a lasting effect in mesenchymal stem cells.

2021-03-16 | GSE113844 | GEO

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