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histone H3.2

Lisa B Caruso, Kayla A Martin, Elisabetta Lauretti, Michael Hulse, Micheal Siciliano, Lena N Lupey-Green, Aaron Abraham, Tomasz Skorski, Italo Tempera
The enzyme Poly(ADP-ribose) polymerase 1 (PARP1) plays a very important role in the DNA damage response, but its role in numerous aspects is not fully understood. We recently showed that in the absence of DNA damage, PARP1 regulates the expression of the chromatin-modifying enzyme EZH2. Work from other groups has shown that EZH2 participates in the DNA damage response. These combined data suggest that EZH2 could be a target of PARP1 in both untreated and genotoxic agent-treated conditions. In this work we tested the hypothesis that, in response to DNA damage, PARP1 regulates EZH2 activity...
February 13, 2018: Oncotarget
Marc-Werner Dobenecker, Joon Seok Park, Jonas Marcello, Michael T McCabe, Richard Gregory, Steven D Knight, Inmaculada Rioja, Anna K Bassil, Rabinder K Prinjha, Alexander Tarakhovsky
Differentiation and activation of T cells require the activity of numerous histone lysine methyltransferases (HMT) that control the transcriptional T cell output. One of the most potent regulators of T cell differentiation is the HMT Ezh2. Ezh2 is a key enzymatic component of polycomb repressive complex 2 (PRC2), which silences gene expression by histone H3 di/tri-methylation at lysine 27. Surprisingly, in many cell types, including T cells, Ezh2 is localized in both the nucleus and the cytosol. Here we show the presence of a nuclear-like PRC2 complex in T cell cytosol and demonstrate a role of cytosolic PRC2 in T cell antigen receptor (TCR)-mediated signaling...
March 9, 2018: Journal of Experimental Medicine
Hyungwoo Cho, Dok Hyun Yoon, Kyu-Pyo Kim, Kyun-Seop Bae, Won Seog Kim, Hyeon-Seok Eom, Jin Seok Kim, Jung Yong Hong, Seok Jin Kim, Hyewon Lee, Soo-Jeong Kim, Cheolwon Suh
Background The objective of this study was to assess the safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), pharmacokinetics, and anti-tumor efficacy of CKD-581, a novel pan-histone deacetylase inhibitor, in patients with lymphoma or multiple myeloma (MM) refractory to standard therapy. Methods In this phase I study, CKD-581 was intravenously administered on days 1, 8, and 15 of a 28-day cycle. A standard 3 + 3 cohort design was used to determine the MTD. Acetylated histones H3 and H4 in peripheral blood mononuclear cells were measured for pharmacodynamic assessment in a subpopulation of patients...
March 9, 2018: Investigational New Drugs
Santanu Mondal, Sangram S Parelkar, Mitesh Nagar, Paul R Thompson
Protein Arginine deiminases (PADs) play an important role in the pathogenesis of various diseases, including rheumatoid arthritis, multiple sclerosis, lupus, ulcerative colitis and breast cancer. Therefore, the development of PAD-inhibitors has drawn significant research interest in recent years. Herein, we describe the development of the first photoswitchable PAD-inhibitors. These compounds possess an azobenzene photoswitch to optically control PAD activity. Screening of a series of inhibitors structurally similar to BB-Cl-Amidine afforded compounds 1 and 2 as the most promising candidates for the light-controlled inhibition of PAD2; the cis-isomer of 1 is 10-fold more potent than its trans-isomer, whereas the trans-isomer of 2 is 45-fold more potent than the corresponding cis-isomer...
March 8, 2018: ACS Chemical Biology
Almesh Kadakol, Vajir Malek, Santosh Kumar Goru, Anuradha Pandey, Anil Bhanudas Gaikwad
OBJECTIVES: Although cardioprotective effects of telmisartan are well explored, its effects on epigenetic alterations associated with type 2 diabetic (T2D) cardiomyopathy remain unmapped. Thus, the present study was designed to evaluate the potential of esculetin and telmisartan combination to reverse histone posttranslational modifications (PTMs) in curbing T2D cardiomyopathy. MATERIALS AND METHODS: T2D was induced by high-fat diet feeding along with low dose of streptozotocin (35 mg/kg, I...
September 2017: Indian Journal of Pharmacology
Tinchou Li, Mingcheng Lee, Fuming Tsai, Yunhsiang Chen, Yiyin Lin, Maoliang Chen
BACKGROUND: Based on accumulating evidence, the regulation of protein expression by antipsychotic drugs (APDs) might be closely related to the control of psychotic symptoms when these drugs are used to treat mental disorders. The low quantity of nuclear proteins in the cell hinders their detection because signal for rare proteins are masked in most proteomic detection systems. METHODS: Nuclear proteins fractionated from APD-treated B35 cells were labeled with iTRAQ and detected by LC/MS/MS to investigate APD-induced alterations in nuclear protein expression...
March 7, 2018: BMC Pharmacology & Toxicology
Yutaka Mizuno, Kentaro Maemura, Yoshihisa Tanaka, Azumi Hirata, Sugiko Futaki, Hiroki Hamamoto, Kohei Taniguchi, Michihiro Hayashi, Kazuhisa Uchiyama, Masa-Aki Shibata, Yoshinori Otsuki, Yoichi Kondo
Delta-like 3 (DLL3) is a member of the Delta/Serrate/Lag-2 family of ligands for the Notch receptor and plays a role in Notch signaling. We have previously revealed that the expression of DLL3 is silenced by aberrant DNA methylation and that overexpression of DLL3 in the HuH2 hepatocellular carcinoma (HCC) cell line induced apoptosis. In the present study, we first confirmed the methylation of DLL3 in HuH2 cells and analyzed the methylation status of the DLL3 promoter region by bisulfite sequencing. Furthermore, we investigated whether other epigenetic modifications, such as histone acetylation and histone methylation, affected the expression of DLL3...
March 5, 2018: Oncology Reports
Fei Hong, Lu Wan, Jie Liu, Ke Huang, Zhenmeng Xiao, Yingjing Zhang, Chunwei Shi
Liver fibrosis is characterized by deposition of excessive extracellular matrix (ECM). The major source of ECM is activated hepatic stellate cells (HSCs). Previously, we reported that hypoxia-inducible factor-1 (Hif-1) regulates activation of HSCs through autophagy. In current work, human HSC cell line LX-2 was used as cell model. It was determined that trimethylation of H3 histone on lysine 4 (H3K4me3) occurred in the Hif-1 transcriptional complex. Inhibition of modifications of histone methylation suppressed Hif-1 nuclear transport, autophagosome formation, and activation of LX-2 cells...
March 2018: FEBS Open Bio
Ting Wang, Beibei Mao, Chi Cheng, Zhuangzhi Zou, Junling Gao, Yanglu Yang, Tong Lei, Xiaolong Qi, Zengqiang Yuan, Wentong Xu, Zhongbing Lu
The transcriptional co-activator Yes-associated protein (YAP) has been implicated as an oncogene and is found to promote breast cancer metastasis. However, the pro-metastatic mechanism of YAP remains unclear. Here, we demonstrated that YAP functions as a transcriptional repressor of growth differentiation factor-15 (GDF15), a divergent member of the transforming growth factor superfamily, in several breast cancer cell lines. Functionally, knockdown of YAP decreased, whereas knockdown of GDF15 increased, the metastatic potential of breast cancer cells...
February 27, 2018: Biochimica et Biophysica Acta
Hong Ding, Wen Chao Lu, Jun Chi Hu, Yu-Chih Liu, Chen Hua Zhang, Fu Lin Lian, Nai Xia Zhang, Fan Wang Meng, Cheng Luo, Kai Xian Chen
SET7, serving as the only histone methyltransferase that monomethylates 'Lys-4' of histone H3, has been proved to function as a key regulator in diverse biological processes, such as cell proliferation, transcriptional network regulation in embryonic stem cell, cell cycle control, protein stability, heart morphogenesis and development. What's more, SET7 is involved inthe pathogenesis of alopecia aerate, breast cancer, tumor and cancer progression, atherosclerosis in human carotid plaques, chronic renal diseases, diabetes, obesity, ovarian cancer, prostate cancer, hepatocellular carcinoma, and pulmonary fibrosis...
March 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Agnieszka Bochyńska, Juliane Lüscher-Firzlaff, Bernhard Lüscher
Regulation of gene expression is achieved by sequence-specific transcriptional regulators, which convey the information that is contained in the sequence of DNA into RNA polymerase activity. This is achieved by the recruitment of transcriptional co-factors. One of the consequences of co-factor recruitment is the control of specific properties of nucleosomes, the basic units of chromatin, and their protein components, the core histones. The main principles are to regulate the position and the characteristics of nucleosomes...
March 2, 2018: Cells
Jisu Yang, Nivedita Chatterjee, Youngho Kim, Ji-Yeon Roh, Jung-Hwan Kwon, Myung-Sook Park, Jinhee Choi
As part of a study to explore the long-term effects of the Hebei Spirit oil spill accident, transgenerational toxicity and associated epigenetic changes were investigated in the nematode Caenorhabditis elegans. Under experimental conditions, worms were exposed to Iranian heavy crude oil (IHC) under three different scenarios: partial early-life exposure (PE), partial late-life exposure (PL), and whole-life exposure (WE). Growth, reproduction, and histone methylation were monitored in the exposed parental worms (P0) and in three consecutive unexposed offspring generations (F1-3 )...
February 21, 2018: Chemosphere
Toshia R Myers, Pier Giorgio Amendola, Yvonne C Lussi, Anna Elisabetta Salcini
Post-translational modifications of histones, constitutive components of chromatin, regulate chromatin compaction and control all DNA-based cellular processes. C. elegans JMJD-1.2, a member of the KDM7 family, is a demethylase active towards several lysine residues on Histone 3 (H3), but its contribution in regulating histone methylation in germ cells has not been fully investigated. Here, we show that jmjd-1.2 is expressed abundantly in the germline where it controls the level of histone 3 lysine 9, lysine 23 and lysine 27 di-methylation (H3K9/K23/K27me2) both in mitotic and meiotic cells...
February 28, 2018: Scientific Reports
Jonas W Højfeldt, Anne Laugesen, Berthe M Willumsen, Helene Damhofer, Lin Hedehus, Andrey Tvardovskiy, Faizaan Mohammad, Ole N Jensen, Kristian Helin
Polycomb repressive complex 2 (PRC2) catalyzes methylation on lysine 27 of histone H3 (H3K27) and is required for maintaining transcriptional patterns and cellular identity, but the specification and maintenance of genomic PRC2 binding and H3K27 methylation patterns remain incompletely understood. Epigenetic mechanisms have been proposed, wherein pre-existing H3K27 methylation directs recruitment and regulates the catalytic activity of PRC2 to support its own maintenance. Here we investigate whether such mechanisms are required for specifying H3K27 methylation patterns in mouse embryonic stem cells (mESCs)...
February 26, 2018: Nature Structural & Molecular Biology
Hiroshi Otsuka, Kenichi Kohashi, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yuichi Yamada, Hidetaka Yamamoto, Yasuharu Nakashima, Yoshinao Oda
The histological definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is quite difficult because the morphological features are not specific and no useful immunohistochemical marker has been identified. Loss-of-function mutations in EED or SUZ12, which encode the core subunit of polycomb repressive complex 2 (PRC2), were reported in MPNSTs, and the mutations were shown to cause inactivation of PRC2, leading to loss of trimethylation of histone H3 at lysine 27 (H3K27me3). Immunohistochemistry of H3K27me3 is expected to be a specific marker for MPNSTs...
January 31, 2018: Pathology, Research and Practice
Hyeryung Yoon, Jungil Yang, Wanqi Liang, Dabing Zhang, Gynheung An
Flower organ patterning is accomplished by spatial and temporal functioning of various regulatory genes. We previously reported that Oryza sativa VIN3-LIKE 2 ( OsVIL2 ) induces flowering by mediating the trimethylation of Histone H3 on LFL1 chromatin. In this study, we report that OsVIL2 also plays crucial roles during spikelet development. Two independent lines of T-DNA insertional mutants in the gene displayed altered organ numbers and abnormal morphology in all spikelet organs. Scanning electron microscopy showed that osvil2 affected organ primordia formation during early spikelet development...
2018: Frontiers in Plant Science
Abdalla Ahmed, Tao Wang, Paul Delgado-Olguin
The neonatal mouse heart has the remarkable capacity to regenerate lost myocardium within the first week of life. Neonatal cardiomyocytes re-express fetal genes that control cell proliferation after injury to promote regeneration. The loss of regenerative capacity of the heart one week after birth coincides with repression of a fetal transcriptional program coordinated by epigenetic regulators. The histone methyltransferase enhancer of zeste homolog 2 (Ezh2) is a repressor of fetal cardiac transcriptional programs and suppresses cardiomyocyte cell proliferation, suggesting a potential function in heart regeneration...
2018: PloS One
Jiamei Lin, Shengqiang Wang, Yunlin Feng, Weihong Zhao, Weilu Zhao, Foquan Luo, Namin Feng
Propofol is widely used in clinical practice, including non-obstetric surgery in pregnant women. Previously, we found that propofol anaesthesia in maternal rats during the third trimester (E18) caused learning and memory impairment to the offspring rats, but how about the exposure during early pregnancy and the underlying mechanisms? Histone acetylation plays an important role in synaptic plasticity. In this study, propofol was administered to the pregnant rats in the early pregnancy (E7). The learning and memory function of the offspring were tested by Morris water maze (MWM) test on post-natal day 30...
February 20, 2018: Journal of Cellular and Molecular Medicine
Wendi Shuai, Jiangxue Wu, Shuai Chen, Ranyi Liu, Zhihua Ye, Chunmei Kuang, Xiang Fu, Gaoyuan Wang, Yingchang Li, Qihua Peng, Wei Shi, Yizhuo Li, Qianghua Zhou, Wenlin Huang
Suppressor of variegation 3-9 homolog 2 (SUV39H2) is a member of the SUV39H subfamily of lysine methyltransferases. Its role in colorectal cancer (CRC) proliferation and metastasis has remained unexplored. Here, we determined that SUV39H2 was upregulated in CRC tissues compared with that in adjacent non-neoplastic tissues. Further statistical analysis revealed that high SUV39H2 expression was strongly associated with distant metastasis (P = 0.016) and TNM stage (P = 0.038) and predicted a shorter overall survival (OS; P = 0...
February 16, 2018: Cancer Letters
M K Sannigrahi, Rajni Sharma, Varinder Singh, Naresh K Panda, Vidya Rattan, Madhu Khullar
INTRODUCTION: Epigenetic modifications have been reported to play an important role in regulating gene expression and these modifications become critical when they have a role in controlling another important layer of epigenetic regulation namely microRNAs. In the present study, we have identified the microRNAs that may be regulated by promoter DNA methylation and histone acetylation in Human papilloma virus-positive head and neck squamous cell carcinoma. METHODOLOGY: HPV-negative cell line (UPCI:SCC-116) and HPV-16 +ve cell line (UPCI:SCC-090) were treated with methylation inhibitor (5-aza-2'-deoxycytidine, AZA) and acetylation inhibitor (Trichostatin-A, TSA), followed by micro-array analysis...
February 17, 2018: Molecular and Cellular Biochemistry
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