The histone H3 lysine 36 demethylase KDM2A/FBXL11 is essential for germ cell development in male mice
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ABSTRACT:
PROVIDER: PRJNA886665 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR21786700.fastq.gz | Fastqsanger.gz | |||
| SRR21786701_1.fastq.gz | Fastqsanger.gz | |||
| SRR21786701_2.fastq.gz | Fastqsanger.gz | |||
| SRR21786702.fastq.gz | Fastqsanger.gz |
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Project description:KDM2A/FBXL11 is a Jumonji-domain containing lysine demethylase catalyzing the removal of mono- and di-methyl modifications of histone H3 lysine 36. While Kdm2a is required for mouse embryogenesis, its role in adult physiology is unknown. Using conditional deletion approaches, we demonstrate that Kdm2a deficiency causes testicular atrophy and male infertility. Though spermatogonial stem cells were unaffected, proliferating and differentiating spermatogonia suffered from delayed cell cycle progression and apoptosis, which correlated with upregulated expression of several cell cycle inhibitors. Loss of Kdm2a in spermatocytes disrupted progression through meiotic prophase, as shown by impaired chromosome synapsis and processing of meiotic double strand breaks, and by altered chromatin states. Correspondingly, Kdm2a mutant spermatocytes failed to activate numerous genes controlling these processes. RNA-sequencing analyses on purified spermatogonia and spermatocytes showed that during normal spermatogonial differentiation over 700 genes undergo repression, which is controlled by KDM2A. CpG-rich promoter genes upregulated in Kdm2a deficient cells are marked by Polycomb Repressive Complexes (PRC) and associated modifications in wildtype male germ cells, suggesting that KDM2A is required for PRC-mediated repression. Our study thus identifies critical roles for KDM2A in coordinating gene expression programs during spermatogonial differentiation and meiosis, which are essential for male germ cell development.
2025-06-16 | GSE214679 | GEO
Project description:KDM2A/FBXL11 is a Jumonji-domain containing lysine demethylase catalyzing the removal of mono- and di-methyl modifications of histone H3 lysine 36. While Kdm2a is required for mouse embryogenesis, its role in adult physiology is unknown. Using conditional deletion approaches, we demonstrate that Kdm2a deficiency causes testicular atrophy and male infertility. Though spermatogonial stem cells were unaffected, proliferating and differentiating spermatogonia suffered from delayed cell cycle progression and apoptosis, which correlated with upregulated expression of several cell cycle inhibitors. Loss of Kdm2a in spermatocytes disrupted progression through meiotic prophase, as shown by impaired chromosome synapsis and processing of meiotic double strand breaks, and by altered chromatin states. Correspondingly, Kdm2a mutant spermatocytes failed to activate numerous genes controlling these processes. RNA-sequencing analyses on purified spermatogonia and spermatocytes showed that during normal spermatogonial differentiation over 700 genes undergo repression, which is controlled by KDM2A. CpG-rich promoter genes upregulated in Kdm2a deficient cells are marked by Polycomb Repressive Complexes (PRC) and associated modifications in wildtype male germ cells, suggesting that KDM2A is required for PRC-mediated repression. Our study thus identifies critical roles for KDM2A in coordinating gene expression programs during spermatogonial differentiation and meiosis, which are essential for male germ cell development.
2025-06-16 | GSE214680 | GEO
Project description:The histone H3 lysine 36 demethylase KDM2A/FBXL11 is essential for germ cell development in male mice [RRBS]
| PRJNA886675 | ENA
Project description:The histone H3 lysine 36 demethylase KDM2A/FBXL11 is essential for germ cell development in male mice [ChIP-Seq]
| PRJNA886674 | ENA
Project description:The histone H3 lysine 36 demethylase KDM2A/FBXL11 is essential for germ cell development in male mice [RNA-Seq]
| PRJNA886676 | ENA
Project description:Eukaryotic gene expression profiles are largely defined by transcription factors that recognize specific DNA sequences in gene regulatory regions and impact RNA polymerase recruitment and transcription. In addition to specific core promoter regulatory elements, up to 70% of genes in higher eukaryotes are also characterized by an overrepresentation of cytosine/guanine base pairs (CpGs) surrounding promoters and gene regulatory units. These features, called CpG islands, were identified over twenty years ago but there remains little mechanistic evidence to suggest how these enigmatic elements contribute to promoter function, with the exception that they are refractory to epigenetic silencing by DNA methylation. Here we uncover a role for CpG islands in buffering gene regulatory elements from repressive histone H3 lysine 36 methylation by directly recruiting the H3K36 specific lysine demethylase enzyme KDM2A. KDM2A is recruited to CpG islands by a zinc finger CxxC (ZF-CxxC) domain that specifically recognizes CpG DNA and is blocked by DNA methylation. This capacity to sense the epigenetic methylation state of DNA constrains KDM2A to non-methylated CpG islands. Importantly, these observations suggest CpG islands may function to delineate gene regulatory elements from bulk chromatin by recruiting factors that create unique chromatin architecture. This study provides information about binding of lysine demethylase enzyme KDM2A in mouse embryonic stem cells.
2010-04-27 | E-GEOD-18588 | biostudies-arrayexpress
Project description:Transcription factors that bind small DNA motifs embedded in promoters play a central role in controlling gene expression. However, in addition to these elements, up to 70% of genes in higher eukaryotes also have high levels of non-methylated cytosine/guanine base pairs (CpGs) surrounding promoters and gene regulatory units. These features, called CpG islands, were identified over twenty years ago but there remains little mechanistic evidence to suggest how these enigmatic elements contribute to promoter function, with the exception that they are refractory to epigenetic silencing by DNA methylation. Here we show that CpG islands directly recruit the H3K36 specific lysine demethylase enzyme KDM2A. Genome wide analyses by ChIP-seq demonstrated a striking global association of KDM2A with CpG islands. Nucleation of KDM2A at these elements resulted in removal of H3K36 methylation creating CpG island chromatin that is uniquely depleted of this modification. KDM2A utilizes a zinc finger CxxC (ZF-CxxC) domain that specifically recognizes non-methylated CpG DNA and binding is blocked when the CpG DNA is methylated, thus constraining KDM2A to nonmethylated CpG islands. These data expose a remarkably straightforward mechanism through which KDM2A delineates a unique architecture that differentiates CpG island chromatin from bulk chromatin. Two cell lines were used in this study: a control line (LMP) with wildtype levels of KDM2A, and a KDM2A knockdown line (RNAi) in which KDM2A levels were depleted by approximately 60% using an shRNA-based approach. For each cell line, RNA was extracted from cells collected on two different dates (rep1 and rep2).
2010-05-27 | E-GEOD-21201 | biostudies-arrayexpress
Project description:Eukaryotic gene expression profiles are largely defined by transcription factors that recognize specific DNA sequences in gene regulatory regions and impact RNA polymerase recruitment and transcription. In addition to specific core promoter regulatory elements, up to 70% of genes in higher eukaryotes are also characterized by an overrepresentation of cytosine/guanine base pairs (CpGs) surrounding promoters and gene regulatory units. These features, called CpG islands, were identified over twenty years ago but there remains little mechanistic evidence to suggest how these enigmatic elements contribute to promoter function, with the exception that they are refractory to epigenetic silencing by DNA methylation. Here we uncover a role for CpG islands in buffering gene regulatory elements from repressive histone H3 lysine 36 methylation by directly recruiting the H3K36 specific lysine demethylase enzyme KDM2A. KDM2A is recruited to CpG islands by a zinc finger CxxC (ZF-CxxC) domain that specifically recognizes CpG DNA and is blocked by DNA methylation. This capacity to sense the epigenetic methylation state of DNA constrains KDM2A to non-methylated CpG islands. Importantly, these observations suggest CpG islands may function to delineate gene regulatory elements from bulk chromatin by recruiting factors that create unique chromatin architecture.
2010-04-27 | GSE18588 | GEO
Project description:Transcription factors that bind small DNA motifs embedded in promoters play a central role in controlling gene expression. However, in addition to these elements, up to 70% of genes in higher eukaryotes also have high levels of non-methylated cytosine/guanine base pairs (CpGs) surrounding promoters and gene regulatory units. These features, called CpG islands, were identified over twenty years ago but there remains little mechanistic evidence to suggest how these enigmatic elements contribute to promoter function, with the exception that they are refractory to epigenetic silencing by DNA methylation. Here we show that CpG islands directly recruit the H3K36 specific lysine demethylase enzyme KDM2A. Genome wide analyses by ChIP-seq demonstrated a striking global association of KDM2A with CpG islands. Nucleation of KDM2A at these elements resulted in removal of H3K36 methylation creating CpG island chromatin that is uniquely depleted of this modification. KDM2A utilizes a zinc finger CxxC (ZF-CxxC) domain that specifically recognizes non-methylated CpG DNA and binding is blocked when the CpG DNA is methylated, thus constraining KDM2A to nonmethylated CpG islands. These data expose a remarkably straightforward mechanism through which KDM2A delineates a unique architecture that differentiates CpG island chromatin from bulk chromatin.
2010-04-27 | GSE21201 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE18588: CpG islands recruit a histone H3 lysine 36 demethylase [Illumina sequencing data] GSE21201: CpG islands recruit a histone H3 lysine 36 demethylase [Agilent data] Refer to individual Series
2010-04-26 | E-GEOD-21202 | biostudies-arrayexpress