The Experts below are selected from a list of 14790 Experts worldwide ranked by ideXlab platform
Hyun-min Kim - One of the best experts on this subject based on the ideXlab platform.
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fanconi anemia fancm fncm 1 and fancd2 fcd 2 are required for maintaining histone methylation levels and interact with the histone Demethylase lsd1 spr 5 in caenorhabditis elegans
Genetics, 2018Co-Authors: Hyun-min Kim, Sara E Beesesims, Monica P. ColaiácovoAbstract:The histone Demethylase LSD1 was originally discovered by removing methyl groups from di- and monomethylated histone H3 lysine 4 (H3K4me2/1). Several studies suggest that LSD1 plays roles in meiosis as well as in the epigenetic regulation of fertility given that, in its absence, there is evidence of a progressive accumulation of H3K4me2 and increased sterility through generations. In addition to the progressive sterility phenotype observed in the mutants, growing evidence for the importance of histone methylation in the regulation of DNA damage repair has attracted more attention to the field in recent years. However, we are still far from understanding the mechanisms by which histone methylation is involved in DNA damage repair, and only a few studies have focused on the roles of histone Demethylases in germline maintenance. Here, we show that the histone Demethylase LSD1/CeSPR-5 interacts with the Fanconi anemia (FA) protein FANCM/CeFNCM-1 using biochemical, cytological, and genetic analyses. LSD1/CeSPR-5 is required for replication stress-induced S phase-checkpoint activation, and its absence suppresses the embryonic lethality and larval arrest observed in fncm-1 mutants. FANCM/CeFNCM-1 relocalizes upon hydroxyurea exposure and colocalizes with FANCD2/CeFCD-2 and LSD1/CeSPR-5, suggesting coordination between this histone Demethylase and FA components to resolve replication stress. Surprisingly, the FA pathway is required for H3K4me2 maintenance, regardless of the presence of replication stress. Our study reveals a connection between FA and epigenetic maintenance and therefore provides new mechanistic insight into the regulation of histone methylation in DNA repair.
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fanconi anemia fancm fncm 1 and fancd2 fcd 2 are required for maintaining histone methylation levels and interact with the histone Demethylase lsd1 spr 5 in c elegans
bioRxiv, 2018Co-Authors: Hyun-min Kim, Sara E Beesesims, Monica P. ColaiácovoAbstract:The histone Demethylase LSD1 was originally discovered as removing methyl groups from di- and monomethylated histone H3 lysine 4 (H3K4me2/1), and several studies suggest it plays roles in meiosis as well as epigenetic sterility given that in its absence there is evidence of a progressive accumulation of H3K4me2 through generations. In addition to transgenerational sterility, growing evidence for the importance of histone methylation in the regulation of DNA damage repair has attracted more attention to the field in recent years. However, we are still far from understanding the mechanisms by which histone methylation is involved in DNA damage repair and only a few studies have been focused on the roles of histone Demethylases in germline maintenance. Here, we show that the histone Demethylase LSD1/CeSPR-5 is interacting with the Fanconi Anemia (FA) protein FANCM/CeFNCM-1 based on biochemical, cytological and genetic analyses. LSD1/CeSPR-5 is required for replication stress-induced S-phase checkpoint activation and its absence suppresses the embryonic lethality and larval arrest observed in fncm-1 mutants. FANCM/CeFNCM-1 re-localizes upon hydroxyurea exposure and co-localizes with FANCD2/CeFCD-2 and LSD1/CeSPR-5 suggesting coordination between this histone Demethylase and FA components to resolve replication stress. Surprisingly, the FA pathway is required for H3K4me2 maintenance regardless of the presence of replication stress. Our study reveals a connection between Fanconi Anemia and epigenetic maintenance, therefore providing new mechanistic insight into the regulation of histone methylation in DNA repair.
Monica P. Colaiácovo - One of the best experts on this subject based on the ideXlab platform.
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fanconi anemia fancm fncm 1 and fancd2 fcd 2 are required for maintaining histone methylation levels and interact with the histone Demethylase lsd1 spr 5 in caenorhabditis elegans
Genetics, 2018Co-Authors: Hyun-min Kim, Sara E Beesesims, Monica P. ColaiácovoAbstract:The histone Demethylase LSD1 was originally discovered by removing methyl groups from di- and monomethylated histone H3 lysine 4 (H3K4me2/1). Several studies suggest that LSD1 plays roles in meiosis as well as in the epigenetic regulation of fertility given that, in its absence, there is evidence of a progressive accumulation of H3K4me2 and increased sterility through generations. In addition to the progressive sterility phenotype observed in the mutants, growing evidence for the importance of histone methylation in the regulation of DNA damage repair has attracted more attention to the field in recent years. However, we are still far from understanding the mechanisms by which histone methylation is involved in DNA damage repair, and only a few studies have focused on the roles of histone Demethylases in germline maintenance. Here, we show that the histone Demethylase LSD1/CeSPR-5 interacts with the Fanconi anemia (FA) protein FANCM/CeFNCM-1 using biochemical, cytological, and genetic analyses. LSD1/CeSPR-5 is required for replication stress-induced S phase-checkpoint activation, and its absence suppresses the embryonic lethality and larval arrest observed in fncm-1 mutants. FANCM/CeFNCM-1 relocalizes upon hydroxyurea exposure and colocalizes with FANCD2/CeFCD-2 and LSD1/CeSPR-5, suggesting coordination between this histone Demethylase and FA components to resolve replication stress. Surprisingly, the FA pathway is required for H3K4me2 maintenance, regardless of the presence of replication stress. Our study reveals a connection between FA and epigenetic maintenance and therefore provides new mechanistic insight into the regulation of histone methylation in DNA repair.
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fanconi anemia fancm fncm 1 and fancd2 fcd 2 are required for maintaining histone methylation levels and interact with the histone Demethylase lsd1 spr 5 in c elegans
bioRxiv, 2018Co-Authors: Hyun-min Kim, Sara E Beesesims, Monica P. ColaiácovoAbstract:The histone Demethylase LSD1 was originally discovered as removing methyl groups from di- and monomethylated histone H3 lysine 4 (H3K4me2/1), and several studies suggest it plays roles in meiosis as well as epigenetic sterility given that in its absence there is evidence of a progressive accumulation of H3K4me2 through generations. In addition to transgenerational sterility, growing evidence for the importance of histone methylation in the regulation of DNA damage repair has attracted more attention to the field in recent years. However, we are still far from understanding the mechanisms by which histone methylation is involved in DNA damage repair and only a few studies have been focused on the roles of histone Demethylases in germline maintenance. Here, we show that the histone Demethylase LSD1/CeSPR-5 is interacting with the Fanconi Anemia (FA) protein FANCM/CeFNCM-1 based on biochemical, cytological and genetic analyses. LSD1/CeSPR-5 is required for replication stress-induced S-phase checkpoint activation and its absence suppresses the embryonic lethality and larval arrest observed in fncm-1 mutants. FANCM/CeFNCM-1 re-localizes upon hydroxyurea exposure and co-localizes with FANCD2/CeFCD-2 and LSD1/CeSPR-5 suggesting coordination between this histone Demethylase and FA components to resolve replication stress. Surprisingly, the FA pathway is required for H3K4me2 maintenance regardless of the presence of replication stress. Our study reveals a connection between Fanconi Anemia and epigenetic maintenance, therefore providing new mechanistic insight into the regulation of histone methylation in DNA repair.
Charlie D Chen - One of the best experts on this subject based on the ideXlab platform.
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utx loss causes myeloid transformation
Leukemia, 2018Co-Authors: Liting Zheng, Danfeng Zhao, Pu Chen, Wei Wang, Yiqin Wang, Gang Han, Charlie D ChenAbstract:Recurrent somatic loss-of-function mutations in histone Demethylases are frequently detected in cancer. However, whether loss of a histone Demethylase can cause cancer has not been determined. Here, we report that knockout of the histone Demethylase Utx in mice causes a chronic myelomonocytic leukemia (CMML)-like disease with splenomegaly, monocytosis, and extramedullary hematopoiesis. Mutational analysis of patient data indicated that UTX mutations occur simultaneously with TP53 mutations in myeloid malignancies, and combined inactivation of Utx and Trp53 accelerated the development of CMML in a cell-autonomous manner. Utx loss caused increased self-renewal of hematopoietic stem cells and predisposed hematopoietic stem cells to differentiate into myeloid-derived lineages. Transcriptome and chromatin immunoprecipitation analyses revealed that Utx activates key transcriptional factors required for erythroid differentiation by modulating histone H3 lysine 27 and lysine 4 trimethylation. Our results suggest that Utx suppresses CMML formation by controlling hematopoietic stem cell self-renewal and differentiation.
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jarid1b is a histone h3 lysine 4 Demethylase up regulated in prostate cancer
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Yang Xiang, Gang Han, Ziqi Zhu, Zhouchun Peng, Hanqing Lin, Adele Pin Chen, Charlie D ChenAbstract:Histone methylation is a dynamic process that participates in a diverse array of cellular processes and has been found to associate with cancer. Recently, several histone Demethylases have been identified that catalyze the removal of methylation from histone H3 lysine residues. Through bioinformatic and biochemical analysis, we identified JARID1B as a H3K4 Demethylase. Overexpression of JARID1B resulted in loss of tri-, di-, and monomethyl H3K4 but did not affect other histone lysine methylations. In vitro biochemical experiments demonstrated that JARID1B directly catalyzes the demethylation. The enzymatic activity requires the JmjC domain and uses Fe(II) and α-ketoglutarate as cofactors. Furthermore, we found that JARID1B is up-regulated in prostate cancer tissues, compared with benign prostate samples. We also demonstrated that JARID1B associates with androgen receptor and regulates its transcriptional activity. Thus, we identified JARID1B as a Demethylase capable of removing three methyl groups from histone H3 lysine 4 and up-regulated in prostate cancer.
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jmjd3 is a histone h3k27 Demethylase
Cell Research, 2007Co-Authors: Yang Xiang, Gang Han, Ziqi Zhu, Hanqing Lin, Charlie D ChenAbstract:Histone methylation is an important epigenetic phenomenon that participates in a diverse array of cellular processes and has been found to be associated with cancer. Recent identification of several histone Demethylases has proved that histone methylation is a reversible process. Through a candidate approach, we have biochemically identified JMJD3 as an H3K27 Demethylase. Transfection of JMJD3 into HeLa cells caused a specific reduction of trimethyl H3K27, but had no effect on di- and monomethyl H3K27, or histone lysine methylations on H3K4 and H3K9. The enzymatic activity requires the JmjC domain and the conserved histidine that has been suggested to be important for a cofactor binding. In vitro biochemical experiments demonstrated that JMJD3 directly catalyzes the demethylation. In addition, we found that JMJD3 is upregulated in prostate cancer, and its expression is higher in metastatic prostate cancer. Thus, we identified JMJD3 as a Demethylase capable of removing the trimethyl group from histone H3 lysine 27 and upregulated in prostate cancer.
Jiayin Dai - One of the best experts on this subject based on the ideXlab platform.
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effects of pentachlorophenol on the quail coturnix japonica liver detoxification pathway
Chemosphere, 2017Co-Authors: Peng Jiang, Jianshe Wang, Nan Sheng, Dongbing Wei, Jiayin DaiAbstract:Pentachlorophenol (PCP), an extensively used pesticide and biocide, is of critical environmental concern due to its toxicity and recalcitrance to degradation. In this study, the effect of PCP on induction of transcription factors, cytochrome P450 (CYP450) genes, and the antioxidative enzyme system were investigated in the quail liver. A total of 60 (4- to 6-week-old) male quails (Coturnix japonica) were administered 0, 0.05, 0.5, and 5 mg/kg/d PCP orally for 42 d. Following exposure, both absolute and relative liver weights were significantly lower than those of the control. Using gas chromatography-mass spectrometry, PCP accumulation was, from highest to lowest, kidney > liver > muscle for all exposure groups. The expressions of CYP1A5, CYP1B1, CYP2C18, nuclear translocator 1 (ARNT1), and aryl hydrocarbon receptor 1 (AHR1) were induced after PCP treatment, and increases were found in the activities of hepatic superoxide dismutase (SOD) and catalase (CAT), and the content of hepatic malondialdehyde (MDA). In addition, exposure to PCP induced an increase in liver 8-hydroxydeoxyguanosine (8-OHdG) and significantly elevated ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-Demethylase (MROD), and 7-ethoxycoumarin-O-deethylase (ECOD) activity, but decreased that of glutathione peroxidase (GSH-Px), benzyloxyresorufin O-debenzylase (BROD), pentoxyresorufin O-depentylase (PROD), and erythromycin N-Demethylase (END). No significant responses were observed for benzyloxy-trifluoromethyl-coumarin (BFC). The protein level of liver nuclear factor κB (NF-κB) was higher, whereas that of nuclear factor E2-related factor 2 (Nrf2) was lower for exposed quail. These results suggest that PCP affects quail oxidative stress by modulating CYP450 enzymes and nuclear transcription factors.
Julie Secombe - One of the best experts on this subject based on the ideXlab platform.
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the histone Demethylase kdm5 is required for synaptic structure and function at the drosophila neuromuscular junction
Cell Reports, 2021Co-Authors: Helen M Belalcazar, Emily L Hendricks, Sumaira Zamurrad, Faith L W Liebl, Julie SecombeAbstract:Mutations in the genes encoding the lysine Demethylase 5 (KDM5) family of histone Demethylases are observed in individuals with intellectual disability (ID). Despite clear evidence linking KDM5 function to neurodevelopmental pathways, how this family of proteins impacts transcriptional programs to mediate synaptic structure and activity remains unclear. Using the Drosophila larval neuromuscular junction (NMJ), we show that KDM5 is required presynaptically for neuroanatomical development and synaptic function. The Jumonji C (JmjC) domain-encoded histone Demethylase activity of KDM5, which is expected to be diminished by many ID-associated alleles, is required for appropriate synaptic morphology and neurotransmission. The activity of the C5HC2 zinc finger is also required, as an ID-associated mutation in this motif reduces NMJ bouton number, increases bouton size, and alters microtubule dynamics. KDM5 therefore uses Demethylase-dependent and independent mechanisms to regulate NMJ structure and activity, highlighting the complex nature by which this chromatin modifier carries out its neuronal gene-regulatory programs.
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the histone Demethylase kdm5 is required for synaptic structure and function at the drosophila neuromuscular junction
Social Science Research Network, 2020Co-Authors: Helen M Belalcazar, Emily L Hendricks, Sumaira Zamurrad, Faith L W Liebl, Julie SecombeAbstract:Mutations in the genes encoding the KDM5 family of histone Demethylases are observed in individuals with intellectual disability (ID). Despite clear evidence linking KDM5 function to neurodevelopmental pathways, how this family of proteins impacts transcriptional programs to mediate synaptic structure and activity remains unclear. Using the Drosophila larval neuromuscular junction (NMJ), we show that KDM5 is required for neuroanatomical development and synaptic function. The JmjC-domain encoded histone Demethylase activity of KDM5, which is expected to be diminished by many ID-associated alleles and required for appropriate synaptic morphology and neurotransmission. The C5HC2 zinc finger of KDM5 is also involved, as an ID-associated mutation in this motif reduces NMJ bouton number but increases bouton size. KDM5 therefore uses Demethylase-dependent and independent mechanisms to regulate NMJ structure and activity, highlighting the complex nature by which this chromatin modifier carries out its neuronal gene regulatory programs.