Role of the histone demethylase Kdm6b/Jmjd3 in somatic cell reprogramming [ATAC-Seq]
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PROVIDER: PRJNA628934 | ENA |
REPOSITORIES: ENA
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Project description:Role of the histone demethylase Kdm6b/Jmjd3 in somatic cell reprogramming
| PRJNA302168 | ENA
Project description:Somatic cells can be reprogrammed to pluripotent stem cells through the addition of just four transcription factors, OCT4, SOX2, KLF4 and c-MYC (OSKM). Although OSKM initiates reprogramming it is clear that extensive epigenetic remodeling is required to complete reprogramming. Critically, OSKM do not directly activate gene expression but instead recruit co-activators and co-repressors that remodel the local chromatin and in some way make the cells permissive for reprogramming. Consequently understanding how epigenetic co-repressors and co-activators are involved in reprogramming is a critical step in understanding the reprogramming process in detail. In this study we explored the role of the lysine-specific demethylase Kdm6b/Jmjd3 and its role in the reprogramming of somatic cells to pluripotent cells.
2020-07-22 | GSE149500 | GEO
Project description:Somatic cells can be reprogrammed to pluripotent stem cells through the addition of just four transcription factors, OCT4, SOX2, KLF4 and c-MYC (OSKM). Although OSKM initiates reprogramming it is clear that extensive epigenetic remodeling is required to complete reprogramming. Critically, OSKM do not directly activate gene expression but instead recruit co-activators and co-repressors that remodel the local chromatin and in some way make the cells permissive for reprogramming. Consequently understanding how epigenetic co-repressors and co-activators are involved in reprogramming is a critical step in understanding the reprogramming process in detail. In this study we explored the role of the lysine-specific demethylase Kdm6b/Jmjd3 and its role in the reprogramming of somatic cells to pluripotent cells.
2020-07-22 | GSE74998 | GEO
Project description:Somatic cells can be reprogrammed to pluripotent stem cells through the addition of just four transcription factors, OCT4, SOX2, KLF4 and c-MYC (OSKM). Although OSKM initiates reprogramming it is clear that extensive epigenetic remodeling is required to complete reprogramming. Critically, OSKM do not directly activate gene expression but instead recruit co-activators and co-repressors that remodel the local chromatin and in some way make the cells permissive for reprogramming. Consequently understanding how epigenetic co-repressors and co-activators are involved in reprogramming is a critical step in understanding the reprogramming process in detail. In this study we explored the role of the lysine-specific demethylase Kdm6b/Jmjd3 and its role in the reprogramming of somatic cells to pluripotent cells.
2020-07-22 | GSE74997 | GEO
Project description:Autophagy is essential for cellular survival and energy homeostasis under nutrient deprivation. Despite the emerging importance of nuclear events in autophagy regulation, epigenetic control of autophagy gene transcription remains unclear. Here, we identify Jumonji-D3 (JMJD3/KDM6B) histone demethylase as a key epigenetic activator of hepatic autophagy. Upon fasting-induced fibroblast growth factor-21 (FGF21) signaling, JMJD3 epigenetically upregulated global autophagy-network genes, including Tfeb, Atg7, Atgl, and Fgf21, through demethylation of histone H3K27-me3, resulting in autophagy-mediated lipid degradation. Mechanistically, phosphorylation of JMJD3 at Thr-1044 by FGF21 signal-activated PKA increased its nuclear localization and interaction with the nuclear receptor PPARto transcriptionally activate autophagy. Chronic administration of FGF21 in obese mice improved defective autophagy and hepatosteatosis in a JMJD3-dependent manner. Remarkably, in non-alcoholic fatty liver disease patients, hepatic expression of JMJD3, ATG7, LC3, and KL were substantially decreased. These findings demonstrate that FGF21-JMJD3 signaling epigenetically links nutrient deprivation with hepatic autophagy and lipid degradation in mammals
2020-05-26 | PXD015672 | Pride
Project description:Mutations in the JMJD3 (KDM6B) chromatin regulator are causally associated with autism spectrum disorder and syndromic intellectual disability, but the neurodevelopmental roles of this histone 3 lysine 27 (H3K27) demethylase are poorly understood. Neural stem cells (NSCs) in the hippocampal dentate gyrus (DG) generate new granule neurons throughout life, and deficits in DG neurogenesis are associated with cognitive and behavioral problems. Here we show that Jmjd3 is required for the establishment of adult neurogenesis in the mouse DG. Conditional deletion of Jmjd3 in embryonic DG precursors results in an adult hippocampus that is essentially devoid of NSCs. While early postnatal mice with Jmjd3-deletion have near normal numbers of DG NSCs, at later stages, Jmjd3-deleted NSCs fail to propagate normally. In addition to the loss of NSCs during postnatal development, neurogenesis from Jmjd3-deleted NSCs is impaired, corresponding to defective neurogenic gene expression. Without Jmjd3, NeuroD2 and Bcl11b(Ctip2) are not properly expressed and exhibit increased levels of H3K27me3, underscoring the role of Jmjd3 in the regulation of transcription for neuronal differentiation. Thus, these data indicate that Jmjd3 plays dual roles in postnatal DG neurogenesis, being critical for the establishment of the NSC pool as well as the differentiation of young DG granule neurons. More broadly, our results suggest a neurodevelopmental link between JMJD3 mutations and hippocampal dysfunction, providing new insights into how mutations in chromatin regulators may contribute to learning disorders.
2021-04-01 | GSE73706 | GEO
Project description:The JmjC domain containing protein JMJD3/KDM6B catalyses H3K27me3 and H3K27me2 demethylation. JMJD3 appears to be highly regulated at the transcriptional level and is upregulated in response to diverse stimuli such as differentiation inducers and stress signals. Accordingly, JMJD3 has been linked to the regulation of different biological processes such as differentiation of embryonic stem cells, inflammatory responses in macrophages, and induction of cellular senescence via regulation of the INK4A-ARF locus. Here we show here that JMJD3 interacts with the tumour suppressor protein p53. We find that the interaction is dependent on the p53 tetramerization domain. Following DNA damage, JMJD3 is transcriptionally upregulated and by performing genome-wide mapping of JMJD3, we demonstrate that it binds genes involved in basic cellular processes, as well as genes regulating cell cycle, response to stress and apoptosis. Moreover, we find that JMJD3 binding sites show significant overlap with p53 bound promoters and enhancer elements. The binding of JMJD3 to p53 target sites is increased in response to DNA damage, and we demonstrate that the recruitment of JMJD3 to these sites is dependent on p53 expression. Therefore, we propose a model in which JMJD3 is recruited to p53 responsive elements via its interaction with p53 and speculate that JMJD3 could act as a fail-safe mechanism to remove low levels of H3K27me3 and H3K27me2 to allow for efficient acetylation of H3K27. Examination of JMJD3 and p53 genome-wide binding in untreated BJ cells or cells exposed to DNA damage (IR, 10 Gy)
2014-06-11 | E-GEOD-55912 | biostudies-arrayexpress
Project description:Autophagy is essential for cellular survival and energy homeostasis under nutrient deprivation. Despite the emerging importance of nuclear events in autophagy regulation, epigenetic control of autophagy gene transcription remains unclear. Here, we identify Jumonji-D3 (JMJD3/KDM6B) histone demethylase as a key epigenetic activator of hepatic autophagy. Upon fasting-induced fibroblast growth factor-21 (FGF21) signaling, JMJD3 epigenetically upregulated global autophagy-network genes, including Tfeb, Atg7, Atgl, and Fgf21, through demethylation of histone H3K27-me3, resulting in autophagy-mediated lipid degradation. Mechanistically, phosphorylation of JMJD3 at Thr-1044 by FGF21 signal-activated PKA increased its nuclear localization and interaction with the nuclear receptor PPARa to transcriptionally activate autophagy. Chronic administration of FGF21 in obese mice improved defective autophagy and hepatosteatosis in a JMJD3-dependent manner. Remarkably, in non-alcoholic fatty liver disease patients, hepatic expression of JMJD3, ATG7, LC3, and bKL were substantially decreased. These findings demonstrate that FGF21-JMJD3 signaling epigenetically links nutrient deprivation with hepatic autophagy and lipid degradation in mammals.
2019-10-01 | GSE138157 | GEO
Project description:This study reports role of Jmjd3/kdm6b in female reproduction and provides a molecular insight of how Jmjd3/kdm6b regulates ovarian function and fertility in mice
2022-01-29 | GSE195498 | GEO
Project description:The JmjC domain containing protein JMJD3/KDM6B catalyses H3K27me3 and H3K27me2 demethylation. JMJD3 appears to be highly regulated at the transcriptional level and is upregulated in response to diverse stimuli such as differentiation inducers and stress signals. Accordingly, JMJD3 has been linked to the regulation of different biological processes such as differentiation of embryonic stem cells, inflammatory responses in macrophages, and induction of cellular senescence via regulation of the INK4A-ARF locus. Here we show here that JMJD3 interacts with the tumour suppressor protein p53. We find that the interaction is dependent on the p53 tetramerization domain. Following DNA damage, JMJD3 is transcriptionally upregulated and by performing genome-wide mapping of JMJD3, we demonstrate that it binds genes involved in basic cellular processes, as well as genes regulating cell cycle, response to stress and apoptosis. Moreover, we find that JMJD3 binding sites show significant overlap with p53 bound promoters and enhancer elements. The binding of JMJD3 to p53 target sites is increased in response to DNA damage, and we demonstrate that the recruitment of JMJD3 to these sites is dependent on p53 expression. Therefore, we propose a model in which JMJD3 is recruited to p53 responsive elements via its interaction with p53 and speculate that JMJD3 could act as a fail-safe mechanism to remove low levels of H3K27me3 and H3K27me2 to allow for efficient acetylation of H3K27.
2014-06-11 | GSE55912 | GEO