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H3K9me3

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https://www.readbyqxmd.com/read/29774127/paf1-complex-interactions-with-setdb1-mediate-promoter-h3k9-methylation-and-transcriptional-repression-of-hoxa9-and-meis1-in-acute-myeloid-leukemia
#1
James Ropa, Nirmalya Saha, Zhiling Chen, Justin Serio, Wei Chen, Dattatreya Mellacheruvu, Lili Zhao, Venkatesha Basrur, Alexey I Nesvizhskii, Andrew G Muntean
The Polymerase Associated Factor 1 complex (PAF1c) is an epigenetic co-modifying complex that directly contacts RNA polymerase II (RNAPII) and several epigenetic regulating proteins. Mutations, overexpression and loss of expression of subunits of the PAF1c are observed in various forms of cancer suggesting proper regulation is needed for cellular development. However, the biochemical interactions with the PAF1c that allow dynamic gene regulation are unclear. We and others have shown that the PAF1c makes a direct interaction with MLL fusion proteins, which are potent oncogenic drivers of acute myeloid leukemia (AML)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29766333/treatment-of-donor-cells-with-recombinant-kdm4d-protein-improves-preimplantation-development-of-cloned-ovine-embryos
#2
Yumei Zhang, Qianqian Wang, Kailing Liu, Enen Gao, Hong Guan, Jian Hou
Incomplete epigenetic reprogramming is one of the major factors affecting the development of embryos cloned by somatic cell nuclear transfer (SCNT). Histone 3 lysine 9 (H3K9) trimethylation has been identified as a key barrier to efficient reprogramming by SCNT. The aim of this study was to explore a method of downregulating H3K9me3 levels in donor cells by using histone lysine demethylase (KDM) protein. When sheep fetal fibroblast cells were treated with recombinant human KDM4D protein (rhKDM4D), the levels of H3K9 trimethylation and dimethylation were both significantly decreased...
May 15, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29765031/comprehensive-epigenetic-landscape-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#3
Rizi Ai, Teresina Laragione, Deepa Hammaker, David L Boyle, Andre Wildberg, Keisuke Maeshima, Emanuele Palescandolo, Vinod Krishna, David Pocalyko, John W Whitaker, Yuchen Bai, Sunil Nagpal, Kurtis E Bachman, Richard I Ainsworth, Mengchi Wang, Bo Ding, Percio S Gulko, Wei Wang, Gary S Firestein
Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29738972/steroids-from-ganoderma-sinense-as-new-natural-inhibitors-of-cancer-associated-mutant-idh1
#4
Mengzhu Zheng, Ruotian Tang, Yue Deng, Kaiyin Yang, Lixia Chen, Hua Li
Isocitrate dehydrogenase (IDH) is one of the key enzymes in the tricarboxylic acid cycle, and IDH mutations have been associated with many cancers, including glioblastoma, sarcoma, acute myeloid leukemia, etc. Three natural steroids 1-3 from Ganoderma sinense, a unique and rare edible-medicinal fungi in China, were found as potential IDH1 inhibitors by virtual ligand screening method. Among the three compounds, 3 showed the highest binding affinity to IDH1 with significant calculated binding free energy. Enzymatic kinetics demonstrated that 3 inhibited mutant enzyme in a noncompetitive manner...
April 30, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29730439/a-metadynamic-approach-to-understand-the-recognition-mechanism-of-the-histone-h3-tail-with-the-atrx-add-domain
#5
Radha Charan Dash, Angela M Zaino, M Kyle Hadden
The binding affinity between the histone 3 (H3) tail and the ADD domain of ATRX (ATRXADD ) increases with the subsequent addition of methyl groups on lysine 9 on H3. To improve our understanding of how the difference in methylation state affects binding between H3 and the ATRXADD , we adopted a metadynamic approach to explore the recognition mechanism between the two proteins and identify the key intermolecular interactions that mediate this protein-peptide interaction (PPI). The non-methylated H3 peptide is recognized only by the PHD finger of ATRXADD while mono-, di-, and trimethylated H3 is recognized by both the PHD and GATA-like zinc finger of the domain...
May 3, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29718303/the-kdm4a-kdm4c-nf-%C3%AE%C2%BAb-and-wdr5-epigenetic-cascade-regulates-the-activation-of-b-cells
#6
Kuo-Hsuan Hung, Yong H Woo, I-Ying Lin, Chin-Hsiu Liu, Li-Chieh Wang, Hsin-Yu Chen, Bor-Luen Chiang, Kuo-I Lin
T follicular helper (Tfh) cell-derived signals promote activation and proliferation of antigen-primed B cells. It remains unclear whether epigenetic regulation is involved in the B cell responses to Tfh cell-derived signals. Here, we demonstrate that Tfh cell-mimicking signals induce the expression of histone demethylases KDM4A and KDM4C, and the concomitant global down-regulation of their substrates, H3K9me3/me2, in B cells. Depletion of KDM4A and KDM4C potentiates B cell activation and proliferation in response to Tfh cell-derived signals...
April 30, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29716892/human-proislet-peptide-promotes-pancreatic-progenitor-cells-to-ameliorate-diabetes-via-foxo1-menin-mediated-epigenetic-regulation
#7
Zongzhe Jiang, Diwen Shi, Yifan Tu, Jingjing Tian, Wenjian Zhang, Bowen Xing, Jihua Wang, Suhuan Liu, Jinning Lou, Jan-Åke Gustafsson, Xianxin Hua, Xiaosong Ma
In this study, we investigated how human proislet peptide (HIP) regulates differentiation of human fetus-derived pancreatic progenitor cells (HFPPCs), and explored the potential link between HIP signaling and the menin pathway, a key pathway that regulates differentiation of pancreatic islets. Our data showed that HIP promoted expression of pro-islet transcription factors (TFs) including PDX-1, MAFA and NKX6.1 as well as other maturation markers of β-cells such as insulin, GLUT2, KIR6.2, SUR1 and VDCC. Moreover, HIP increased insulin content, and promoted the ability of HFPPCs to normalize the blood glucose in diabetic mice...
May 1, 2018: Diabetes
https://www.readbyqxmd.com/read/29703894/a-somatic-role-for-the-histone-methyltransferase-setdb1-in-endogenous-retrovirus-silencing
#8
Masaki Kato, Keiko Takemoto, Yoichi Shinkai
Subsets of endogenous retroviruses (ERVs) are derepressed in mouse embryonic stem cells (mESCs) deficient for Setdb1, which catalyzes histone H3 lysine 9 trimethylation (H3K9me3). Most of those ERVs, including IAPs, remain silent if Setdb1 is deleted in differentiated embryonic cells; however they are derepressed when deficient for Dnmt1, suggesting that Setdb1 is dispensable for ERV silencing in somatic cells. However, H3K9me3 enrichment on ERVs is maintained in differentiated cells and is mostly diminished in mouse embryonic fibroblasts (MEFs) lacking Setdb1...
April 27, 2018: Nature Communications
https://www.readbyqxmd.com/read/29686265/reprogramming-of-h3k9me3-dependent-heterochromatin-during-mammalian-embryo-development
#9
Chenfei Wang, Xiaoyu Liu, Yawei Gao, Lei Yang, Chong Li, Wenqiang Liu, Chuan Chen, Xiaochen Kou, Yanhong Zhao, Jiayu Chen, Yixuan Wang, Rongrong Le, Hong Wang, Tao Duan, Yong Zhang, Shaorong Gao
H3K9me3-dependent heterochromatin is a major barrier of cell fate changes that must be reprogrammed after fertilization. However, the molecular details of these events are lacking in early embryos. Here, we map the genome-wide distribution of H3K9me3 modifications in mouse early embryos. We find that H3K9me3 exhibits distinct dynamic features in promoters and long terminal repeats (LTRs). Both parental genomes undergo large-scale H3K9me3 reestablishment after fertilization, and the imbalance in parental H3K9me3 signals lasts until blastocyst...
May 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29685391/interactions-of-hp1-bound-to-h3k9me3-dinucleosome-by-molecular-simulations-and-biochemical-assays
#10
Shuhei Watanabe, Yuichi Mishima, Masahiro Shimizu, Isao Suetake, Shoji Takada
Heterochromatin protein 1 (HP1), associated with heterochromatin formation, recognizes an epigenetically repressive marker, trimethylated lysine 9 in histone H3 (H3K9me3), and generally contributes to long-term silencing. How HP1 induces heterochromatin is not fully understood. Recent experiments suggested that not one, but two nucleosomes provide a platform for this recognition. Integrating previous and new biochemical assays with computational modeling, we provide near-atomic structural models for HP1 binding to the dinucleosomes...
April 20, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29682202/ctcf-kdm4a-complex-correlates-with-histone-modifications-that-negatively-regulate-chd5-gene-expression-in-cancer-cell-lines
#11
Lissania Guerra-Calderas, Rodrigo González-Barrios, Carlos César Patiño, Nicolás Alcaraz, Marisol Salgado-Albarrán, David Cantú de León, Clementina Castro Hernández, Yesennia Sánchez-Pérez, Héctor Aquiles Maldonado-Martínez, Inti A De la Rosa-Velazquez, Fernanda Vargas-Romero, Luis A Herrera, Alejandro García-Carrancá, Ernesto Soto-Reyes
Histone demethylase KDM4A is involved in H3K9me3 and H3K36me3 demethylation, which are epigenetic modifications associated with gene silencing and RNA Polymerase II elongation, respectively. KDM4A is abnormally expressed in cancer, affecting the expression of multiple targets, such as the CHD5 gene. This enzyme localizes at the first intron of CHD5 , and the dissociation of KDM4A increases gene expression. In vitro assays showed that KDM4A-mediated demethylation is enhanced in the presence of CTCF, suggesting that CTCF could increase its enzymatic activity in vivo, however the specific mechanism by which CTCF and KDM4A might be involved in the CHD5 gene repression is poorly understood...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29682190/the-jmjn-domain-as-a-dimerization-interface-and-a-targeted-inhibitor-of-kdm4-demethylase-activity
#12
May Levin, Michal Stark, Yehuda G Assaraf
Histone methylation is regulated to shape the epigenome by modulating DNA compaction, thus playing central roles in fundamental chromatin-based processes including transcriptional regulation, DNA repair and cell proliferation. Histone methylation is erased by demethylases including the well-established KDM4 subfamily members, however, little is known about their dimerization capacity and its impact on their demethylase activity. Using the powerful bimolecular fluorescence complementation technique, we herein show the in situ formation of human KDM4A and KDM4C homodimers and heterodimers in nuclei of live transfectant cells and evaluate their H3K9me3 demethylation activity...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29670078/terra-recruitment-of-polycomb-to-telomeres-is-essential-for-histone-trymethylation-marks-at-telomeric-heterochromatin
#13
Juan J Montero, Isabel López-Silanes, Diego Megías, Mario F Fraga, Álvaro Castells-García, Maria A Blasco
TERRAs are long non-coding RNAs generated from the telomeres. Lack of TERRA knockout models has hampered understanding TERRAs' functions. We recently identified chromosome 20q as one of the main origins of human TERRAs, allowing us to generate the first 20q-TERRA knockout models and to demonstrate that TERRAs are essential for telomere length maintenance and protection. Here, we use ALT 20q-TERRA knockout cells to address a direct role of TERRAs in telomeric heterochromatin formation. We find that 20q-TERRAs are essential for the establishment of H3K9me3, H4K20me3, and H3K27me3 heterochromatin marks at telomeres...
April 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29665845/deletion-of-hp1%C3%AE-in-cardiac-myocytes-affects-h4k20me3-levels-but-does-not-impact-cardiac-growth
#14
Kyohei Oyama, Danny El-Nachef, Chen Fang, Hidemi Kajimoto, Jeremy P Brown, Prim B Singh, W Robb MacLellan
BACKGROUND: Heterochromatin, which is formed when tri-methyl lysine 9 of histone H3 (H3K9me3) is bound by heterochromatin 1 proteins (HP1s), plays an important role in differentiation and senescence by silencing cell cycle genes. Cardiac myocytes (CMs) accumulate heterochromatin during differentiation and demethylation of H3K9me3 inhibits cell cycle gene silencing and cell cycle exit in CMs; however, it is unclear if this process is mediated by HP1s. In this study, we created a conditional CM-specific HP1 gamma (HP1γ) knockout (KO) mouse model and tested whether HP1γ is required for cell cycle gene silencing and cardiac growth...
April 17, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29661885/the-long-non-coding-rna-paupar-promotes-kap1-dependent-chromatin-changes-and-regulates-olfactory-bulb-neurogenesis
#15
Ioanna Pavlaki, Farah Alammari, Bin Sun, Neil Clark, Tamara Sirey, Sheena Lee, Dan J Woodcock, Chris P Ponting, Francis G Szele, Keith W Vance
Many long non-coding RNAs (lncRNAs) are expressed during central nervous system (CNS) development, yet their in vivo roles and mechanisms of action remain poorly understood. Paupar , a CNS-expressed lncRNA, controls neuroblastoma cell growth by binding and modulating the activity of transcriptional regulatory elements in a genome-wide manner. We show here that the Paupar lncRNA directly binds KAP1, an essential epigenetic regulatory protein, and thereby regulates the expression of shared target genes important for proliferation and neuronal differentiation...
April 16, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29648536/silencing-of-transposable-elements-may-not-be-a-major-driver-of-regulatory-evolution-in-primate-ipscs
#16
Michelle C Ward, Siming Zhao, Kaixuan Luo, Bryan J Pavlovic, Mohammad M Karimi, Matthew Stephens, Yoav Gilad
Transposable elements (TEs) comprise almost half of primate genomes and their aberrant regulation can result in deleterious effects. In pluripotent stem cells, rapidly-evolving KRAB-ZNF genes target TEs for silencing by H3K9me3. To investigate the evolution of TE silencing, we performed H3K9me3 ChIP-seq experiments in induced pluripotent stem cells from ten human and seven chimpanzee individuals. We identified four million orthologous TEs and found the SVA and ERV families to be marked most frequently by H3K9me3...
April 12, 2018: ELife
https://www.readbyqxmd.com/read/29625135/effect-of-heterochromatin-stability-on-intestinal-stem-cell-aging-in-drosophila
#17
Ho-Jun Jeon, Young-Shin Kim, Joong-Gook Kim, Kyu Heo, Jung-Hoon Pyo, Masamitsu Yamaguchi, Joung-Sun Park, Mi-Ae Yoo
Chromatin change is one of the crucial causes of aging. Specifically, maintenance of heterochromatin stability is critical for cellular integrity, and its loss induces genomic instability and cellular aging. However, the causes and effects of heterochromatin instability in multicellular tissue aging still remain unclear. Here, in the adult Drosophila midgut, we report age-related loss of heterochromatin stability in enterocytes (ECs) due to the loss and dispersion of tri-methylated histone H3 Lys9 (H3K9me3) and heterochromatin protein 1 (HP1)...
April 3, 2018: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29624717/sirt3-restricts-hbv-transcription-and-replication-via-epigenetic-regulation-of-cccdna-involving-suv39h1-and-setd1a-histone-methyltransferases
#18
Ji-Hua Ren, Jie-Li Hu, Sheng-Tao Cheng, Hai-Bo Yu, Vincent Kam Wai Wong, Betty Yuen Kwan Law, Yong-Feng Yang, Ying Huang, Yi Liu, Wei-Xian Chen, Xue-Fei Cai, Hua Tang, Yuan Hu, Wen-Lu Zhang, Xiang Liu, Quan-Xin Long, Li Zhou, Na-Na Tao, Hong-Zhong Zhou, Qiu-Xia Yang, Fang Ren, Lin He, Rui Gong, Ai-Long Huang, Juan Chen
Hepatitis B virus (HBV) infection remains a major health problem worldwide. Maintenance of the covalently closed circular DNA (cccDNA) which serves as a template for HBV RNA transcription is responsible for the failure of eradicating chronic HBV during current antiviral therapy. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications. In this study, we identified SIRT3 as a host factor restricting HBV transcription and replication by screening seven members of Sirtuin family which is the class III histone deacetylase...
April 6, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29610526/zinc-finger-protein-471-suppresses-gastric-cancer-through-transcriptionally-repressing-downstream-oncogenic-pls3-and-tfap2a
#19
Lei Cao, Shiyan Wang, Yanquan Zhang, Ka-Chun Wong, Geicho Nakatsu, Xiaohong Wang, Sunny Wong, Jiafu Ji, Jun Yu
Zinc-finger protein 471 (ZNF471) was preferentially methylated in gastric cancer using promoter methylation array. The role of ZNF471 in human cancer is unclear. Here we elucidated the functional significance, molecular mechanisms and clinical impact of ZNF471 in gastric cancer. ZNF471 mRNA was silenced in 15 out of 16 gastric cancer cell lines due to promoter hypermethylation. Significantly higher ZNF471 promoter methylation was also observed in primary gastric cancers compared to their adjacent normal tissues (P < 0...
April 3, 2018: Oncogene
https://www.readbyqxmd.com/read/29602239/inflammatory-factor-receptor-toll-like-receptor-4-controls-telomeres-through-heterochromatin-protein-1-isoforms-in-liver-cancer-stem-cell
#20
Qidi Zheng, Jie Xu, Zhuojia Lin, Yanan Lu, Xiaoru Xin, Xiaonan Li, Yuxin Yang, Qiuyu Meng, Chen Wang, Wujun Xiong, Dongdong Lu
Toll-like receptor 4 (TLR4) which acts as a receptor for lipopolysaccharide (LPS) has been reported to be involved in carcinogenesis. However, the regulatory mechanism of it has not been elucidated. Herein, we demonstrate that TLR4 promotes the malignant growth of liver cancer stem cells. Mechanistically, TLR4 promotes the expression of histone-lysine N-methyltransferase (SUV39 h2) and increases the formation of trimethyl histone H3 lysine 9-heterochromatin protein 1-telomere repeat binding factor 2 (H3K9me3-HP1-TRF2) complex at the telomeric locus under mediation by long non coding RNA urothelial cancer-associated 1 (CUDR)...
March 30, 2018: Journal of Cellular and Molecular Medicine
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