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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
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...
September 9, 2016: Drug Metabolism and Pharmacokinetics
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
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...
September 16, 2016: Journal of Steroid Biochemistry and Molecular Biology
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
Santosh Kumar Goru, Almesh Kadakol, Anuradha Pandey, Vajir Malek, Nisha Sharma, Anil Bhanudas Gaikwad
Hyperglycaemia-induced expression of extracellular matrix (ECM) components plays a major role in the development diabetic nephropathy (DN). The epigenetic mechanisms that modulate ECM gene expression in DN remain unclear. Therefore, we examined the role of histone H2A and H2B mono-ubiquitination on epigenetic chromatin marks such as histone H3 lysine dimethylation (H3K4Me2, H3K9Me2 and H3K79Me2) in type 1 diabetic rat kidney. Hyperglycaemia increased collagen deposition and Col1a1 gene expression. In whole kidney of diabetic animals, both H2AK119 mono-ubiquitination (H2AK119Ub) and H2BK120 mono-ubiquitination (H2BK120Ub) were found to be increased whereas, in glomeruli of diabetic animals expression of both H2AK119Ub and H2BK120Ub were reduced...
August 31, 2016: Biochemical Journal
Chan-Wei Yu, Vivian Hsiu-Chuan Liao
Arsenic is a prevalent environmental toxin. Arsenic is associated with a wide variety of adverse effects; however, studies on whether As-induced toxicities can be transferred from parents to offspring have received little attention. Caenorhabditis elegans has become an important animal model in biomedical and environmental toxicology research. In this study, transgenerational reproductive toxicity by arsenite exposure and the underlying mechanisms in C. elegans were investigated over six generations (F0-F5)...
October 4, 2016: Environmental Science & Technology
Chongzhi Zang, Annouck Luyten, Justina Chen, X Shirley Liu, Ramesh A Shivdasani
Mutations in mouse and human Nfe2, Fli1 and Runx1 cause thrombocytopenia. We applied genome-wide chromatin dynamics and ChIP-seq to determine these transcription factors' (TFs) activities in terminal megakaryocyte (MK) maturation. Enhancers with H3K4me2-marked nucleosome pairs were most enriched for NF-E2, FLI and RUNX sequence motifs, suggesting that this TF triad controls much of the late MK program. ChIP-seq revealed NF-E2 occupancy near previously implicated target genes, whose expression is compromised in Nfe2-null cells, and many other genes that become active late in MK differentiation...
2016: Scientific Reports
Ryan Rickels, Deqing Hu, Clayton K Collings, Ashley R Woodfin, Andrea Piunti, Man Mohan, Hans-Martin Herz, Evgeny Kvon, Ali Shilatifard
Polycomb response elements (PREs) are specific DNA sequences that stably maintain the developmental pattern of gene expression. Drosophila PREs are well characterized, whereas the existence of PREs in mammals remains debated. Accumulating evidence supports a model in which CpG islands recruit Polycomb group (PcG) complexes; however, which subset of CGIs is selected to serve as PREs is unclear. Trithorax (Trx) positively regulates gene expression in Drosophila and co-occupies PREs to antagonize Polycomb-dependent silencing...
July 21, 2016: Molecular Cell
Nicolas Diotel, Yohann Mérot, Pascal Coumailleau, Marie-Madeleine Gueguen, Aurélien A Sérandour, Gilles Salbert, Olivier Kah
The epigenetic mark 5-hydroxymethylcytosine (5hmC) is a cytosine modification that is abundant in the central nervous system of mammals and which results from 5-methylcytosine oxidation by TET enzymes. Such a mark is suggested to play key roles in the regulation of chromatin structure and gene expression. However, its precise functions still remain poorly understood and information about its distribution in non-mammalian species is still lacking. Here, the distribution of 5hmC was investigated in the brain of adult zebrafish, African claw frog and mouse in a comparative manner...
July 14, 2016: Journal of Comparative Neurology
Rana Mainpal, Judith L Yanowitz
The molecular pathways that govern how germ line fate is acquired is an area of intense investigation that has major implications for the development of assisted reproductive technologies, infertility interventions, and treatment of germ cell cancers. Transcriptional repression has emerged as a primary mechanism to ensure suppression of somatic growth programs in primordial germ cells. In this commentary, we address how xnd-1 illuminates our understanding of transcriptional repression and how it is coordinated with the germ cell differentiation program...
April 2016: Worm
Wassim Eid, Wafaa Abdel-Rehim
Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by defined factors, which provide a powerful basis for personalized stem-cell based therapies. However, cellular reprogramming is an inefficient and metabolically demanding process commonly associated with obstacles that hamper further use of this technology. Spontaneous differentiation of iPS cells cultures represents a significant hurdle that hinder obtaining high quality iPS cells for further downstream experimentation. In this study, we found that a natural compound, vitamin C, augmented pluripotency in iPS cells and reduced unwanted spontaneous differentiation during iPS cells maintenance...
June 25, 2016: Biological Chemistry
Agustina D'Urso, Yoh-Hei Takahashi, Bin Xiong, Jessica Marone, Robert Coukos, Carlo Randise-Hinchliff, Ji-Ping Wang, Ali Shilatifard, Jason H Brickner
In yeast and humans, previous experiences can lead to epigenetic transcriptional memory: repressed genes that exhibit mitotically heritable changes in chromatin structure and promoter recruitment of poised RNA polymerase II preinitiation complex (RNAPII PIC), which enhances future reactivation. Here, we show that INO1 memory in yeast is initiated by binding of the Sfl1 transcription factor to the cis-acting Memory Recruitment Sequence, targeting INO1 to the nuclear periphery. Memory requires a remodeled form of the Set1/COMPASS methyltransferase lacking Spp1, which dimethylates histone H3 lysine 4 (H3K4me2)...
2016: ELife
Qiaoyan Guo, Xiaoxia Li, Hongbo Han, Chaoyuan Li, Shujun Liu, Wenhui Gao, Guangdong Sun
Transforming growth factor beta1- (TGF-β1-) induced p21-dependent mesangial cell (MC) hypertrophy plays a key role in the pathogenesis of chronic renal diseases including diabetic nephropathy (DN). Increasing evidence demonstrated the role of posttranscriptional modifications (PTMs) in the event; however, the precise regulatory mechanism of histone lysine methylation remains largely unknown. Here, we examined the roles of both histone H3 lysine 4 and lysine 9 methylations (H3K4me/H3K9me) in TGF-β1 induced p21 gene expression in rat mesangial cells (RMCs)...
2016: BioMed Research International
Aseel Eid, Syed Waseem Bihaqi, William E Renehan, Nasser H Zawia
INTRODUCTION: Early life lead (Pb) exposure results in a latent increase in Alzheimer's disease (AD)-related proteins, and cognitive deficits late in life in both rodents and primates. This study was conducted to investigate if these late life changes were accompanied by epigenetic alterations. METHODS: Western blot analysis and RT-PCR were used to measure Deoxyribonucleic acid methylation regulators (DNMT1, DNMT3a, MeCP2, MAT2A) and histone proteins (H3K9Ac, H3K4me2, H3K27me3)...
2016: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Ho-Ryun Chung, Chao Xu, Alisa Fuchs, Andreas Mund, Martin Lange, Hannah Staege, Tobias Schubert, Chuanbing Bian, Ilona Dunkel, Anton Eberharter, Catherine Regnard, Henrike Klinker, David Meierhofer, Luca Cozzuto, Andreas Winterpacht, Luciano Di Croce, Jinrong Min, Hans Will, Sarah Kinkley
PHF13 is a chromatin affiliated protein with a functional role in differentiation, cell division, DNA damage response and higher chromatin order. To gain insight into PHF13's ability to modulate these processes, we elucidate the mechanisms targeting PHF13 to chromatin, its genome wide localization and its molecular chromatin context. Size exclusion chromatography, mass spectrometry, X-ray crystallography and ChIP sequencing demonstrate that PHF13 binds chromatin in a multivalent fashion via direct interactions with H3K4me2/3 and DNA, and indirectly via interactions with PRC2 and RNA PolII...
2016: ELife
Unmesh Jadhav, Kodandaramireddy Nalapareddy, Madhurima Saxena, Nicholas K O'Neill, Luca Pinello, Guo-Cheng Yuan, Stuart H Orkin, Ramesh A Shivdasani
Bivalent promoters in embryonic stem cells (ESCs) carry methylation marks on two lysine residues, K4 and K27, in histone3 (H3). K4me2/3 is generally considered to promote transcription, and Polycomb Repressive Complex 2 (PRC2) places K27me3, which is erased at lineage-restricted genes when ESCs differentiate in culture. Molecular defects in various PRC2 null adult tissues lack a unifying explanation. We found that epigenomes in adult mouse intestine and other self-renewing tissues show fewer and distinct bivalent promoters compared to ESCs...
June 2, 2016: Cell
Evan J Kyzar, Huaibo Zhang, Amul J Sakharkar, Subhash C Pandey
Alcohol exposure in adolescence is an important risk factor for the development of alcoholism in adulthood. Epigenetic processes are implicated in the persistence of adolescent alcohol exposure-related changes, specifically in the amygdala. We investigated the role of histone methylation mechanisms in the persistent effects of adolescent intermittent ethanol (AIE) exposure in adulthood. Adolescent rats were exposed to 2 g/kg ethanol (2 days on/off) or intermittent n-saline (AIS) during postnatal days (PND) 28-41 and used for behavioral and epigenetic studies...
May 15, 2016: Addiction Biology
S A LaMere, R C Thompson, H K Komori, A Mark, D R Salomon
The epigenetic determinants driving the responses of CD4 T cells to antigen are currently an area of active research. Much has been done to characterize helper T-cell subsets and their associated genome-wide epigenetic patterns. In contrast, little is known about the dynamics of histone modifications during CD4 T-cell activation and the differential kinetics of these epigenetic marks between naive and memory T cells. In this study, we have detailed the dynamics of genome-wide promoter H3K4me2 and H3K4me3 over a time course during activation of human naive and memory CD4 T cells...
July 2016: Genes and Immunity
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
Hypoxia is an environmental stress at high altitude and underground conditions but it is also present in many chronic age-related diseases, where blood flow into tissues is impaired. The oxygen-sensing system stimulates gene expression protecting tissues against hypoxic insults. Hypoxia stabilizes the expression of hypoxia-inducible transcription factor-1α (HIF-1α), which controls the expression of hundreds of survival genes related to e.g. enhanced energy metabolism and autophagy. Moreover, many stress-related signaling mechanisms, such as oxidative stress and energy metabolic disturbances, as well as the signaling cascades via ceramide, mTOR, NF-κB, and TGF-β pathways, can also induce the expression of HIF-1α protein to facilitate cell survival in normoxia...
March 2016: Aging and Disease
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