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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
Jianing Zhong, Xianfeng Li, Wanshi Cai, Yan Wang, Shanshan Dong, Jie Yang, Jian'an Zhang, Nana Wu, Yuanyuan Li, Fengbiao Mao, Cheng Zeng, Jinyu Wu, Xingzhi Xu, Zhong Sheng Sun
The Ten Eleven Translocation 1 (TET1) protein is a DNA demethylase that regulates gene expression through altering statue of DNA methylation. However, recent studies have demonstrated that TET1 could modulate transcriptional expression independent of its DNA demethylation activity; yet, the detailed mechanisms underlying TET1's role in such transcriptional regulation remain not well understood. Here, we uncovered that Tet1 formed a chromatin complex with histone acetyltransferase Mof and scaffold protein Sin3a in mouse embryonic stem cells by integrative genomic analysis using publicly available ChIP-seq data sets and a series of in vitro biochemical studies in human cell lines...
October 12, 2016: Nucleic Acids Research
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
Shafqat Ali Khan, Ramchandra Amnekar, Bharat Khade, Savio George Barreto, Mukta Ramadwar, Shailesh V Shrikhande, Sanjay Gupta
BACKGROUND: Alterations in histone modifications are now well known to result in epigenetic heterogeneity in tumor tissues; however, their prognostic value and association with resection margins still remain poorly understood and controversial. Further, histopathologically negative resection margins in several cancers have been associated with better prognosis of the disease. However, in gastric cancer, despite a high rate of R0 resection, a considerably high incidence of loco-regional recurrence is observed...
2016: Clinical Epigenetics
David M Nelson, Farah Jaber-Hijazi, John J Cole, Neil A Robertson, Jeffrey S Pawlikowski, Kevin T Norris, Steven W Criscione, Nikolay A Pchelintsev, Desiree Piscitello, Nicholas Stong, Taranjit Singh Rai, Tony McBryan, Gabriel L Otte, Colin Nixon, William Clark, Harold Riethman, Hong Wu, Gunnar Schotta, Benjamin A Garcia, Nicola Neretti, Duncan M Baird, Shelley L Berger, Peter D Adams
BACKGROUND: Histone modification H4K20me3 and its methyltransferase SUV420H2 have been implicated in suppression of tumorigenesis. The underlying mechanism is unclear, although H4K20me3 abundance increases during cellular senescence, a stable proliferation arrest and tumor suppressor process, triggered by diverse molecular cues, including activated oncogenes. Here, we investigate the function of H4K20me3 in senescence and tumor suppression. RESULTS: Using immunofluorescence and ChIP-seq we determine the distribution of H4K20me3 in proliferating and senescent human cells...
2016: Genome Biology
Caitlin G Howe, Mary V Gamble
Arsenic is a human carcinogen and also increases the risk for non-cancer outcomes. Arsenic-induced epigenetic dysregulation may contribute to arsenic toxicity. Although there are several reviews on arsenic and epigenetics, these have largely focused on DNA methylation. Here, we review investigations of the effects of arsenic on global levels of histone posttranslational modifications (PTMs). Multiple studies have observed that arsenic induces higher levels of H3 lysine 9 dimethylation (H3K9me2) and also higher levels of H3 serine 10 phosphorylation (H3S10ph), which regulate chromosome segregation...
September 2016: Current Environmental Health Reports
Ji-Young Kim, Jindan Yu, Sarki A Abdulkadir, Debabrata Chakravarti
Androgen receptor (AR) plays pivotal roles in prostate cancer. Upon androgen stimulation, AR recruits the Protein kinase N1 (PKN1), which phosphorylates histone H3 at threonine 11, with subsequent recruitment of tryptophan, aspartic acid (WD) repeat-containing protein 5 (WDR5) and the su(var)3-9, enhancer of zeste, trithorax/mixed-lineage leukemia (SET1/MLL) histone methyltransferase complex to promote AR target gene activation and prostate cancer cell growth. However, the underlying mechanisms of target gene activation and cell growth subsequent to WDR5 recruitment are not well understood...
August 2016: Molecular Endocrinology
Raz Bar-Ziv, Yoav Voichek, Naama Barkai
Chromatin is composed of DNA and histones, which provide a unified platform for regulating DNA-related processes, mostly through their post-translational modification. During DNA replication, histone arrangement is perturbed, first to allow progression of DNA polymerase and then during repackaging of the replicated DNA. To study how DNA replication influences the pattern of histone modification, we followed the cell-cycle dynamics of 10 histone marks in budding yeast. We find that histones deposited on newly replicated DNA are modified at different rates: While some marks appear immediately upon replication (e...
September 2016: Genome Research
Kalpana Mujoo, Clayton R Hunt, Nobuo Horikoshi, Tej K Pandita
MOF (males absent on the first) was initially identified as a dosage compensation factor in Drosophila that acetylates lysine 16 of histone H4 (H4K16ac) and increased gene transcription from the single copy male X-chromosome. In humans, however, the ortholog of Drosophila MOF has been shown to interact with a range of proteins that extend its potential significance well beyond transcription. For example, recent results indicate MOF is an upstream regulator of the ATM (ataxia-telangiectasia mutated) protein, the loss of which is responsible for ataxia telangiectasia (AT)...
March 30, 2016: Mechanisms of Ageing and Development
Xiaoru Zhang, Thomas Kluz, Lisa Gesumaria, Mary S Matsui, Max Costa, Hong Sun
Ultraviolet radiation (UVR) from sunlight is the primary effector of skin DNA damage. Chromatin remodeling and histone post-translational modification (PTM) are critical factors in repairing DNA damage and maintaining genomic integrity, however, the dynamic changes of histone marks in response to solar UVR are not well characterized. Here we report global changes in histone PTMs induced by solar simulated UVR (ssUVR). A decrease in lysine acetylation of histones H3 and H4, particularly at positions of H3 lysine 9, lysine 56, H4 lysine 5, and lysine 16, was found in human keratinocytes exposed to ssUVR...
2016: PloS One
Qinhong Wang, Michael Goldstein
Recent reports have demonstrated that DNA double-strand break (DSB)-induced small RNAs (diRNA) play an important role in the DNA damage response (DDR). However, the molecular mechanism by which diRNAs regulate the DDR remains unclear. Here, we report that Dicer- and Drosha-dependent diRNAs function as guiding molecules to promote the recruitment of the methyltransferase MMSET (WHSC1) and the acetyltransferase Tip60 (KAT5) to the DSB, where local levels of histone H4 di- and tri-methylation at lysine 20 (H4K20me2, 3) and H4 acetylation at lysine 16 (H4K16Ac) were enhanced...
April 1, 2016: Cancer Research
Sofía T Menéndez, M Ángeles Villaronga, Juan P Rodrigo, Saúl Álvarez-Teijeiro, Rocío G Urdinguio, Mario F Fraga, Carlos Suárez, Juana M García-Pedrero
Evidences indicate that HERG1 voltage-gated potassium channel is frequently aberrantly expressed in various cancers including head and neck squamous cell carcinomas (HNSCC), representing a clinically and biologically relevant feature during disease progression and a potential therapeutic target. The present study further and significantly extends these data investigating for the first time the expression and individual contribution of HERG1 isoforms, their clinical significance during disease progression and also the underlying regulatory mechanisms...
2016: Scientific Reports
Sreerangam N C V L Pushpavalli, Arpita Sarkar, M Janaki Ramaiah, G Koteswara Rao, Indira Bag, Utpal Bhadra, Manika Pal-Bhadra
Histone modulations have been implicated in various cellular and developmental processes where in Drosophila Mof is involved in acetylation of H4K16. Reduction in the size of larval imaginal discs is observed in the null mutants of mof with increased apoptosis. Deficiency involving Hid, Reaper and Grim [H99] alleviated mof (RNAi) induced apoptosis in the eye discs. mof (RNAi) induced apoptosis leads to activation of caspases which is suppressed by over expression of caspase inhibitors like P35 and Diap1 clearly depicting the role of caspases in programmed cell death...
March 2016: Apoptosis: An International Journal on Programmed Cell Death
Santanu Adhikary, Sulagna Sanyal, Moitri Basu, Isha Sengupta, Sabyasachi Sen, Dushyant Kumar Srivastava, Siddhartha Roy, Chandrima Das
ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8), a newly identified component of the transcriptional coregulator network, was found to interact with the Nucleosome Remodeling and Deacetylase (NuRD) complex. Previous reports have shown that ZMYND8 is instrumental in recruiting the NuRD complex to damaged chromatin for repressing transcription and promoting double strand break repair by homologous recombination. However, the mode of transcription regulation by ZMYND8 has remained elusive...
February 5, 2016: Journal of Biological Chemistry
Li Lu, Xiangsong Chen, Dean Sanders, Shuiming Qian, Xuehua Zhong
Histone acetylation and deacetylation are key epigenetic gene regulatory mechanisms that play critical roles in eukaryotes. Acetylation of histone 4 lysine 16 (H4K16ac) is implicated in many cellular processes. However, its biological function and relationship with transcription are largely unexplored in plants. We generated first genome-wide high-resolution maps of H4K16ac in Arabidopsis thaliana and Oryza sativa. We showed that H4K16ac is preferentially enriched around the transcription start sites and positively correlates with gene expression levels...
2015: Epigenetics: Official Journal of the DNA Methylation Society
Jin Sun, Hui-Min Wei, Jiang Xu, Jian-Feng Chang, Zhihao Yang, Xingjie Ren, Wen-Wen Lv, Lu-Ping Liu, Li-Xia Pan, Xia Wang, Huan-Huan Qiao, Bing Zhu, Jun-Yuan Ji, Dong Yan, Ting Xie, Fang-Lin Sun, Jian-Quan Ni
Epigenetics plays critical roles in controlling stem cell self-renewal and differentiation. Histone H1 is one of the most critical chromatin regulators, but its role in adult stem cell regulation remains unclear. Here we report that H1 is intrinsically required in the regulation of germline stem cells (GSCs) in the Drosophila ovary. The loss of H1 from GSCs causes their premature differentiation through activation of the key GSC differentiation factor bam. Interestingly, the acetylated H4 lysine 16 (H4K16ac) is selectively augmented in the H1-depleted GSCs...
2015: Nature Communications
Da Liu, Donglu Wu, Linhong Zhao, Yang Yang, Jian Ding, Liguo Dong, Lianghai Hu, Fei Wang, Xiaoming Zhao, Yong Cai, Jingji Jin
Histone post-translational modification heritably regulates gene expression involved in most cellular biological processes. Experimental studies suggest that alteration of histone modifications affects gene expression by changing chromatin structure, causing various cellular responses to environmental influences. Arsenic (As), a naturally occurring element and environmental pollutant, is an established human carcinogen. Recently, increasing evidence suggests that As-mediated epigenetic mechanisms may be involved in its toxicity and carcinogenicity, but how this occurs is still unclear...
2015: PloS One
Yu-Long Jin, Bao-Xia Dong, Li Xu, Hai-Long Tang, Guang-Xun Gao, Hong-Tao Gu, Mi-Mi Shu, Xie-Qun Chen
OBJECTIVE: To explore the effect of valproic acid(VPA) on anti-myeloma activity of Doxorubicin(DOX) or Melphalan(MEL) and its related mechanism. METHODS: Human multiple myeloma(MM) cells were treated with VPA of non-toxic dose in absence and presence of DOX or MEL at different concentrations (ie. IC10, IC20, IC40). The cell proliferation was detected by MTT method. Western blot was used to detect the expression levels of autophagy-related proteins (LC3, ATG5, ATG7) and acetylated histone H4K16ac...
June 2015: Zhongguo Shi Yan Xue Ye Xue za Zhi
Qi Zhou, Doris Bachtrog
Sex chromosomes evolve distinctive types of chromatin from a pair of ancestral autosomes that are usually euchromatic. In Drosophila, the dosage-compensated X becomes enriched for hyperactive chromatin in males (mediated by H4K16ac), while the Y chromosome acquires silencing heterochromatin (enriched for H3K9me2/3). Drosophila autosomes are typically mostly euchromatic but the small dot chromosome has evolved a heterochromatin-like milieu (enriched for H3K9me2/3) that permits the normal expression of dot-linked genes, but which is different from typical pericentric heterochromatin...
June 2015: PLoS Genetics
Xupeng Mu, Shaohua Yan, Changhao Fu, Anhui Wei
Histone modification plays an important role in maintaining pluripotency and self-renewal of embryonic stem cells (ESCs). The histone acetyltransferase MOF is a key regulator of ESCs; however, the role of MOF in the process of reprogramming back to induced pluripotent stem cells (iPSCs) remains unclear. In this study, we investigated the function of MOF on the generation of iPSCs. We show that iPSCs contain high levels of MOF mRNA, and the expression level of MOF protein is dramatically upregulated following reprogramming...
August 2015: Cellular Reprogramming
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