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https://www.readbyqxmd.com/read/28289232/transcriptional-landscape-of-the-human-cell-cycle
#1
Yin Liu, Sujun Chen, Su Wang, Fraser Soares, Martin Fischer, Feilong Meng, Zhou Du, Charles Lin, Clifford Meyer, James A DeCaprio, Myles Brown, X Shirley Liu, Housheng Hansen He
Steady-state gene expression across the cell cycle has been studied extensively. However, transcriptional gene regulation and the dynamics of histone modification at different cell-cycle stages are largely unknown. By applying a combination of global nuclear run-on sequencing (GRO-seq), RNA sequencing (RNA-seq), and histone-modification Chip sequencing (ChIP-seq), we depicted a comprehensive transcriptional landscape at the G0/G1, G1/S, and M phases of breast cancer MCF-7 cells. Importantly, GRO-seq and RNA-seq analysis identified different cell-cycle-regulated genes, suggesting a lag between transcription and steady-state expression during the cell cycle...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28284523/demethylase-kdm6a-epigenetically-promotes-il-6-and-ifn-%C3%AE-production-in-macrophages
#2
Xia Li, Qian Zhang, Qingzhu Shi, Yin Liu, Kai Zhao, Qicong Shen, Yang Shi, Xingguang Liu, Chunmei Wang, Nan Li, Yuanfang Ma, Xuetao Cao
Molecular regulation of innate signal-initiated proinflammatory cytokine production has been extensively investigated. However, the roles of epigenetic modifiers and their underlying mechanisms in regulating innate inflammatory response and development of autoimmune diseases need to be further understood. Demethylase Kdm6a promotes gene transcription in cell-lineage specification through demethylating histone H3 lysine di/tri-methylation (H3K27me2/3), and loss of Kdm6a results in developmental defects. However, the function of Kdm6a in innate immunity and inflammation remains largely unknown...
March 8, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28266526/elf-mf-exposure-affects-the-robustness-of-epigenetic-programming-during-granulopoiesis
#3
Melissa Manser, Mohamad R Abdul Sater, Christoph D Schmid, Faiza Noreen, Manuel Murbach, Niels Kuster, David Schuermann, Primo Schär
Extremely-low-frequency magnetic fields (ELF-MF) have been classified as "possibly carcinogenic" to humans on the grounds of an epidemiological association of ELF-MF exposure with an increased risk of childhood leukaemia. Yet, underlying mechanisms have remained obscure. Genome instability seems an unlikely reason as the energy transmitted by ELF-MF is too low to damage DNA and induce cancer-promoting mutations. ELF-MF, however, may perturb the epigenetic code of genomes, which is well-known to be sensitive to environmental conditions and generally deranged in cancers, including leukaemia...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219005/a-rhodium-iii-based-inhibitor-of-lysine-specific-histone-demethylase-1-as-an-epigenetic-modulator-in-prostate-cancer-cells
#4
Chao Yang, Wanhe Wang, Jia-Xin Liang, Guodong Li, Kasipandi Vellaisamy, Chun-Yuen Wong, Dik-Lung Ma, Chung-Hang Leung
We report herein a novel rhodium(III) complex 1 as a new LSD1 targeting agent and epigenetic modulator. Complex 1 disrupted the interaction of LSD1-H3K4me2 in human prostate carcinoma cells and enhanced the amplification of p21, FOXA2, and BMP2 gene promoters. Complex 1 was selective for LSD1 over other histone demethylases, such as KDM2b, KDM7, and MAO activities, and also showed antiproliferative activity toward human cancer cells. To date, complex 1 is the first metal-based inhibitor of LSD1 activity.
March 1, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28209170/lincrnafezf1-as1-represses-p21-expression-to-promote-gastric-cancer-proliferation-through-lsd1-mediated-h3k4me2-demethylation
#5
Yan-Wen Liu, Rui Xia, Kai Lu, Min Xie, Fen Yang, Ming Sun, Wei De, Cailian Wang, Guozhong Ji
BACKGROUND: Although the prognosis of gastric cancer patients have a favorable progression, there are some patients with unusual patterns of locoregional and systemic recurrence. Therefore, a better understanding of early molecular events of the disease is needed. Current evidences demonstrate that long noncoding RNAs (lncRNAs) may be an important class of functional regulators involved in human gastric cancers development. Our previous studies suggest that HOTAIR contributes to gastric cancer development, and the overexpression of HOTAIR predicts a poor prognosis...
February 16, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28194553/acidic-domains-differentially-read-histone-h3-lysine-4-methylation-status-and-are-widely-present-in-chromatin-associated-proteins
#6
Meng Wu, Wei Wei, Jiwei Chen, Rong Cong, Tieliu Shi, Jiwen Li, Jiemin Wong, James X Du
Histone methylation is believed to provide binding sites for specific reader proteins, which translate histone code into biological function. Here we show that a family of acidic domain-containing proteins including nucleophosmin (NPM1), pp32, SET/TAF1β, nucleolin (NCL) and upstream binding factor (UBF) are novel H3K4me2-binding proteins. These proteins exhibit a unique pattern of interaction with methylated H3K4, as their binding is stimulated by H3K4me2 and inhibited by H3K4me1 and H3K4me3. These proteins contain one or more acidic domains consisting mainly of aspartic and/or glutamic residues that are necessary for preferential binding of H3K4me2...
February 13, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28102760/phf13-a-new-player-involved-in-rna-polymerase-ii-transcriptional-regulation-and-co-transcriptional-splicing
#7
Alisa Fuchs, Marcos Torroba, Sarah Kinkley
We recently identified PHF13 as an H3K4me2/3 chromatin reader and transcriptional co-regulator. We found that PHF13 interacts with RNAPIIS5P and PRC2 stabilizing their association with active and bivalent promoters. Furthermore, mass spectrometry analysis identified ∼50 spliceosomal proteins in PHF13s interactome. Here, we will discuss the potential role of PHF13 in RNAPII pausing and co-transcriptional splicing.
January 19, 2017: Transcription
https://www.readbyqxmd.com/read/27999197/effects-of-lipopolysaccharide-on-maturation-of-bovine-oocyte-in-vitro-and-its-possible-mechanisms
#8
Shan-Jiang Zhao, Yun-Wei Pang, Xue-Ming Zhao, Wei-Hua Du, Hai-Sheng Hao, Hua-Bin Zhu
Lipopolysaccharide disturbs the secretion of gonadotropin, endometrial function and implantation efficiency. However, there is little information regarding the effects of lipopolysaccharide on cyclic ovary activity, especially oocyte maturation. Therefore, we aimed to investigate the effects of lipopolysaccharide on the maturation potential of bovine oocytes. We found that lipopolysaccharide exposure significantly decreased the first polar body extrusion rate and delayed the cell cycle progression. The abnormal spindle rate was significantly increased in lipopolysaccharide treatment group, accompanied by disrupted localization and level of phosphorylated mitogen-activated protein kinase (p-MAPK)...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926873/foxa1-directs-h3k4-monomethylation-at-enhancers-via-recruitment-of-the-methyltransferase-mll3
#9
Kamila M Jozwik, Igor Chernukhin, Aurelien A Serandour, Sankari Nagarajan, Jason S Carroll
FOXA1 is a pioneer factor that binds to enhancer regions that are enriched in H3K4 mono- and dimethylation (H3K4me1 and H3K4me2). We performed a FOXA1 rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) screen in ERα-positive MCF-7 breast cancer cells and found histone-lysine N-methyltransferase (MLL3) as the top FOXA1-interacting protein. MLL3 is typically thought to induce H3K4me3 at promoter regions, but recent findings suggest it may contribute to H3K4me1 deposition. We performed MLL3 chromatin immunoprecipitation sequencing (ChIP-seq) in breast cancer cells, and MLL3 was shown to occupy regions marked by FOXA1 occupancy and H3K4me1 and H3K4me2...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27910233/a-genetically-encoded-allysine-for-the-synthesis-of-proteins-with-site-specific-lysine-dimethylation
#10
Zhipeng A Wang, Yu Zeng, Yadagiri Kurra, Xin Wang, Jeffery M Tharp, Erol C Vatansever, Willie W Hsu, Susie Dai, Xinqiang Fang, Wenshe R Liu
Using the amber suppression approach, N(ϵ) -(4-azidobenzoxycarbonyl)-δ,ϵ-dehydrolysine, an allysine precursor is genetically encoded in E. coli. Its genetic incorporation followed by two sequential biocompatible reactions allows convenient synthesis of proteins with site-specific lysine dimethylation. Using this approach, dimethyl-histone H3 and p53 proteins have been synthesized and used to probe functions of epigenetic enzymes including histone demethylase LSD1 and histone acetyltransferase Tip60. We confirmed that LSD1 is catalytically active toward H3K4me2 and H3K9me2 but inert toward H3K36me2, and methylation at p53 K372 directly activates Tip60 for its catalyzed acetylation at p53 K120...
January 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/27899379/transcriptional-regulator-cnot3-defines-an-aggressive-colorectal-cancer-subtype
#11
Paloma Cejas, Alessia Cavazza, C N Yandava, Victor Moreno, David Horst, Juan Moreno-Rubio, Emilio Burgos, Marta Mendiola, Len Taing, Ajay Goel, Jaime Feliu, Ramesh A Shivdasani
Cancer cells exhibit dramatic alterations of chromatin organization at cis-regulatory elements, but the molecular basis, extent, and impact of these alterations are still being unraveled. Here, we identify extensive genome-wide modification of sites bearing the active histone mark H3K4me2 in primary human colorectal cancers, as compared with corresponding benign precursor adenomas. Modification of certain colorectal cancer sites highlighted the activity of the transcription factor CNOT3, which is known to control self-renewal of embryonic stem cells (ESC)...
February 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/27894088/lsd1-binds-to-hpv16-e7-and-promotes-the-epithelial-mesenchymal-transition-in-cervical-cancer-by-demethylating-histones-at-the-vimentin-promoter
#12
Yuan Liu, Yanan Wang, Chunqin Chen, Jiawen Zhang, Wenyan Qian, Yu Dong, Zhiqiang Liu, Xi Zhang, Xiaoyun Wang, Zhenbo Zhang, Xiaobing Shi, Sufang Wu
Lysine-specific demethylase 1 (LSD1), which specifically demethylates histone H3 lysine 4 (H3K4) and lysine 9 (H3K9), is dysregulated in several cancers. We found that ectopic expression of LSD1 in cervical cancer cells promoted invasion and metastasis in vitro and in vivo, reduced the expression of the epithelial marker E-cadherin, and induced the expression of the mesenchymal marker, Vimentin. By contrast, LSD1 knockdown had the opposite effect and attenuated the HPV16 E7-induced epithelial-mesenchymal transition (EMT)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27892458/modulation-of-mrna-and-lncrna-expression-dynamics-by-the-set2-rpd3s-pathway
#13
Ji Hyun Kim, Bo Bae Lee, Young Mi Oh, Chenchen Zhu, Lars M Steinmetz, Yookyeong Lee, Wan Kyu Kim, Sung Bae Lee, Stephen Buratowski, TaeSoo Kim
H3K36 methylation by Set2 targets Rpd3S histone deacetylase to transcribed regions of mRNA genes, repressing internal cryptic promoters and slowing elongation. Here we explore the function of this pathway by analysing transcription in yeast undergoing a series of carbon source shifts. Approximately 80 mRNA genes show increased induction upon SET2 deletion. A majority of these promoters have overlapping lncRNA transcription that targets H3K36me3 and deacetylation by Rpd3S to the mRNA promoter. We previously reported a similar mechanism for H3K4me2-mediated repression via recruitment of the Set3C histone deacetylase...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27879032/altered-expression-of-brg1-and-histone-demethylases-and-aberrant-h3k4-methylation-in-less-developmentally-competent-embryos-at-the-time-of-embryonic-genome-activation
#14
Werner G Glanzner, Audrey Wachter, Ana Rita S Coutinho, Marcelo S Albornoz, Raj Duggavathi, Paulo B D GonÇAlves, Vilceu Bordignon
Epigenetics is a fundamental regulator underlying many biological functions, such as development and cell differentiation. Epigenetic modifications affect key chromatin regulation, including transcription and DNA repair, which are critical for normal embryo development. In this study, we profiled the expression of epigenetic modifiers and patterns of epigenetic changes in porcine embryos around the period of embryonic genome activation (EGA). We observed that Brahma-related gene 1 (BRG1) and Lysine demethylase 1A (KDM1A), which can alter the methylation status of lysine 4 in histone 3 (H3K4), localize to the nucleus at Day 3-4 of development...
November 23, 2016: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/27800642/p110%C3%AE-inhibition-reduces-histone-h3k4-di-methylation-in-prostate-cancer
#15
Jun Pang, Yue-Wu Yang, Yiling Huang, Jun Yang, Hao Zhang, Ruibao Chen, Liang Dong, Yan Huang, Dongying Wang, Jihong Liu, Benyi Li
INTRODUCTION AND AIMS: Epigenetic alteration plays a major role in the development and progression of human cancers, including prostate cancer. Histones are the key factors in modulating gene accessibility to transcription factors and post-translational modification of the histone N-terminal tail including methylation is associated with either transcriptional activation (H3K4me2) or repression (H3K9me3). Furthermore, phosphoinositide 3-kinase (PI3 K) signaling and the androgen receptor (AR) are the key determinants in prostate cancer development and progression...
November 1, 2016: Prostate
https://www.readbyqxmd.com/read/27760318/phf20-readers-link-methylation-of-histone-h3k4-and-p53-with-h4k16-acetylation
#16
Brianna J Klein, Xiaoyan Wang, Gaofeng Cui, Chao Yuan, Maria Victoria Botuyan, Kevin Lin, Yue Lu, Xiaolu Wang, Yue Zhao, Christiane J Bruns, Georges Mer, Xiaobing Shi, Tatiana G Kutateladze
PHF20 is a core component of the lysine acetyltransferase complex MOF (male absent on the first)-NSL (non-specific lethal) that generates the major epigenetic mark H4K16ac and is necessary for transcriptional regulation and DNA repair. The role of PHF20 in the complex remains elusive. Here, we report on functional coupling between methylation readers in PHF20. We show that the plant homeodomain (PHD) finger of PHF20 recognizes dimethylated lysine 4 of histone H3 (H3K4me2) and represents an example of a native reader that selects for this modification...
October 18, 2016: Cell Reports
https://www.readbyqxmd.com/read/27727071/developmental-regulation-of-cyp3a4-and-cyp3a7-in-chinese-han-population
#17
Hang He, Ya-Li Nie, Jiang-Feng Li, Xiang-Guang Meng, Wei-Hong Yang, Yu-Long Chen, Shu-Jie Wang, Xiaochao Ma, Quan-Cheng Kan, Li-Rong Zhang
CYP3A4 and CYP3A7 are generally served as the major adult and fetal liver forms, respectively, and exhibited a developmental switch during liver maturation. The objective of this study was to explore the potential mechanisms associated with the developmental switch of CYP3A4 and CYP3A7 in the Chinese Han population. We analyzed CYP3A4/7, nuclear receptors, and epigenetic modifications in human liver samples. We found that the expression levels of CYP3A4 mRNA in adults were significantly higher than the levels in fetus...
December 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27716056/histone-modifications-facilitate-the-coexpression-of-bidirectional-promoters-in-rice
#18
Yuan Fang, Lei Wang, Ximeng Wang, Qi You, Xiucai Pan, Jin Xiao, Xiu-E Wang, Yufeng Wu, Zhen Su, Wenli Zhang
BACKGROUND: Bidirectional gene pairs are highly abundant and mostly co-regulated in eukaryotic genomes. The structural features of bidirectional promoters (BDPs) have been well studied in yeast, humans and plants. However, the underlying mechanisms responsible for the coexpression of BDPs remain understudied, especially in plants. RESULTS: Here, we characterized chromatin features associated with rice BDPs. Several unique chromatin features were present in rice BDPs but were missing from unidirectional promoters (UDPs), including overrepresented active histone marks, canonical nucleosomes and underrepresented H3K27me3...
September 30, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27645313/class-i-lysine-deacetylases-promote-glucocorticoid-induced-transcriptional-repression-through-functional-interaction-with-lsd1
#19
Nina M Patrick, Chanel A Griggs, Ali L Icenogle, Maryam M Gilpatrick, Vineela Kadiyala, Rosa Jaime-Frias, Catharine L Smith
Small molecule inhibitors of lysine deacetylases (KDACs) are approved for clinical use in treatment of several diseases. Nuclear receptors, such as the glucocorticoid receptor (GR) use lysine acetyltransferases (KATs or HATs) and KDACs to regulate transcription through acetylation and deacetylation of protein targets such as histones. Previously we have shown that KDAC1 activity facilitates GR-activated transcription at about half of all cellular target genes. In the current study we examine the role of Class I KDACs in glucocorticoid-mediated repression of gene expression...
March 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27617035/pax6-associates-with-h3k4-specific-histone-methyltransferases-mll1-mll2-and-set1a-and-regulates-h3k4-methylation-at-promoters-and-enhancers
#20
Jian Sun, Yilin Zhao, Rebecca McGreal, Yamit Cohen-Tayar, Shira Rockowitz, Carola Wilczek, Ruth Ashery-Padan, David Shechter, Deyou Zheng, Ales Cvekl
BACKGROUND: Pax6 is a key regulator of the entire cascade of ocular lens formation through specific binding to promoters and enhancers of batteries of target genes. The promoters and enhancers communicate with each other through DNA looping mediated by multiple protein-DNA and protein-protein interactions and are marked by specific combinations of histone posttranslational modifications (PTMs). Enhancers are distinguished from bulk chromatin by specific modifications of core histone H3, including H3K4me1 and H3K27ac, while promoters show increased H3K4me3 PTM...
2016: Epigenetics & Chromatin
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