DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE54411 | GEO | 2014/07/03
SECONDARY ACCESSION(S): PRJNA236455
REPOSITORIES: GEO
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Project description: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
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Project description:Defective germline reprogramming in Miwi2- and Dnmt3l-deficient mice results in the failure to reestablish transposon silencing, meiotic arrest and progressive loss of spermatogonia. Here we sought to understand the molecular basis for this spermatogonial dysfunction. Through a combination of imaging, conditional genetics and transcriptome analysis, we demonstrate that germ cell elimination in the respective mutants arises due to defective germline reprogramming rather than a function for the respective factors within spermatogonia. In both Miwi2-/- and Dnmt3l-/- spermatogonia the intracisternal-A particle (IAP) family of endogenous retroviruses is de-repressed, but in contrast to meiotic cells DNA damage is not observed. Instead we find that unmethylated IAP promoters rewire the spermatogonial transcriptome by driving expression of neighboring host genes. In summary, defective reprogramming deregulates the spermatogonial transcriptome that may underlie spermatogonial dysfunction.
2018-03-09 | E-MTAB-6202 | biostudies-arrayexpress
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
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
Project description:Spermatogonial differentiation is a developmental process that is essential for spermatogenesis, but the molecular and cellular changes that germ cells must undergo to transition from undifferentiated spermatogonia to differentiating spermatogonia remain largely undefined. Retinoic acid (RA) is necessary and sufficient for spermatogonial differentiation. Using the postnatal mouse testis, we examine the transcriptome changes that accompany spermatogonial differentiation. Spermatogenesis was synchronized by administration of potent and selective RA synthesis inhibitor; as a result, testes contained only undifferentiated spermatogonia. Then, the inhibitor was discontinued, and mice were given a single dose of exogenous RA to initiate spermatogonial differentiation. We measured transcriptomes in FACS-enriched germ cells either before RA administration, when the cells correspond to Aal spermatogonia (and a minor contribution of spermatogonial stem cells) or at two points after RA administration, when the cells correspond to A1 or A3 differentiating spermatogonia. The results of this study reveal the full transcriptome changes accompanying spermatogonial differentiation in the mouse.
2023-07-03 | GSE213716 | GEO
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. Total RNA extracted from shGFP or shDnmt3L (three different) embryonic stem cells. A duplicate was performed for each point. Cells were transfected with shRNA and selected with Puromicin for 3 days before RNA extraction
2013-09-27 | E-GEOD-44643 | biostudies-arrayexpress
Project description:In mouse, spermatogonial stem/progenitor cells are the progenitor cell which develop to mature sperms through a series of mitotic and meiotic divisions and differentiation. Gfra1 is an established surface marker for mouse spermatogonial stem/progenitor cells. In this study, we used a transcriptomic approach to investigate the effect of aging on Gfra1-positive and -negative populations of mouse male germ cells. Spermatogonial stem/progenitor cells were isolated from testes of mice at ages 6-day, 21-day, 60-day, and 8-months by magnetic assisted cell sorting (MACS) technique using Gfra1 marker. Transcriptomes among different ages and Gfra1 status were compared.
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Project description:DNA methylation is generally known to inactivate gene expression. The DNA methyltransferases (DNMTs), DNMT3A and DNMT3B, catalyze somatic cell lineage-specific DNA methylation, while DNMT3A and DNMT3L catalyze germ cell lineage-specific DNA methylation. How such lineage- and gene-specific DNA methylation patterns are created remains to be elucidated. To better understand the regulatory mechanisms underlying DNA methylation, we generated transgenic mice that constitutively expressed DNMT3A and DNMT3L, and analyzed DNA methylation, gene expression, and their subsequent impact on ontogeny. All transgenic mice were born normally but died within 20 weeks accompanied with cardiac hypertrophy. Several genes were repressed in the hearts of transgenic mice compared with those in wild-type mice. CpG islands of these downregulated genes were highly methylated in the transgenic mice. This abnormal methylation occurred in the perinatal stage. Conversely, mono-allelic DNA methylation at imprinted loci was faithfully maintained in all transgenic mice, except H19. Thus, the loci preferred by DNMT3A and DNMT3L differ between somatic and germ cell lineages.
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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
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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