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chromatin interaction

Ozgur Oksuz, Varun Narendra, Chul-Hwan Lee, Nicolas Descostes, Gary LeRoy, Ramya Raviram, Lili Blumenberg, Kelly Karch, Pedro P Rocha, Benjamin A Garcia, Jane A Skok, Danny Reinberg
Polycomb repressive complex 2 (PRC2) maintains gene silencing by catalyzing methylation of histone H3 at lysine 27 (H3K27me2/3) within chromatin. By designing a system whereby PRC2-mediated repressive domains were collapsed and then reconstructed in an inducible fashion in vivo, a two-step mechanism of H3K27me2/3 domain formation became evident. First, PRC2 is stably recruited by the actions of JARID2 and MTF2 to a limited number of spatially interacting "nucleation sites," creating H3K27me3-forming Polycomb foci within the nucleus...
June 21, 2018: Molecular Cell
Deepti Deobagkar
Epigenetics confers adaptability and survival advantage to an organism. Most epigenetic processes demonstrate memory and heritability. DNA methylation is an epigenetic process that adds imprints which can be inherited during cell division and across generations. DNA methylation adds an additional level of information to the basic DNA sequence and can influence chromatin organization and the function of the DNA sequence. In bacteria, it works as a defence strategy and preserves genome integrity. DNA methylation in eukaryotes has been implicated in a large number of cellular regulatory processes and is implied in development, differentiation, life style diseases and cancer...
June 2018: Journal of Genetics
Julian M Rozenberg, Joan M Taylor, Christopher P Mack
Given our previous demonstration that RBPJ binds a methylated repressor element and regulates smooth muscle cell (SMC)-specific gene expression, we used genome-wide approaches to identify RBPJ binding regions in human aortic SMC and to assess RBPJ's effects on chromatin structure and gene expression. RBPJ bound to consensus cis elements, but also to TCmGGGA sequences within Alu repeats that were less transcriptionally active as assessed by DNAse hypersensitivity, H3K9 acetylation, and Notch3 and RNA Pol II binding...
June 21, 2018: Nucleic Acids Research
Shuiming Qian, Xinchen Lv, Ray N Scheid, Li Lu, Zhenlin Yang, Wei Chen, Rui Liu, Melissa D Boersma, John M Denu, Xuehua Zhong, Jiamu Du
The ability of a cell to dynamically switch its chromatin between different functional states constitutes a key mechanism regulating gene expression. Histone mark "readers" display distinct binding specificity to different histone modifications and play critical roles in regulating chromatin states. Here, we show a plant-specific histone reader SHORT LIFE (SHL) capable of recognizing both H3K27me3 and H3K4me3 via its bromo-adjacent homology (BAH) and plant homeodomain (PHD) domains, respectively...
June 21, 2018: Nature Communications
Miroslav P Ivanov, Rene Ladurner, Ina Poser, Rebecca Beveridge, Evelyn Rampler, Otto Hudecz, Maria Novatchkova, Jean-Karim Hériché, Gordana Wutz, Petra van der Lelij, Emanuel Kreidl, James Ra Hutchins, Heinz Axelsson-Ekker, Jan Ellenberg, Anthony A Hyman, Karl Mechtler, Jan-Michael Peters
Chromosome segregation depends on sister chromatid cohesion which is established by cohesin during DNA replication. Cohesive cohesin complexes become acetylated to prevent their precocious release by WAPL before cells have reached mitosis. To obtain insight into how DNA replication, cohesion establishment and cohesin acetylation are coordinated, we analysed the interaction partners of 55 human proteins implicated in these processes by mass spectrometry. This proteomic screen revealed that on chromatin the cohesin acetyltransferase ESCO2 associates with the MCM2-7 subcomplex of the replicative Cdc45-MCM-GINS helicase...
June 21, 2018: EMBO Journal
Won-Ki Cho, Jan-Hendrik Spille, Micca Hecht, Choongman Lee, Charles Li, Valentin Grube, Ibrahim I Cisse
Models of gene control have emerged from genetic and biochemical studies, with limited consideration of the spatial organization and dynamics of key components in living cells. Here we used live cell super-resolution and light sheet imaging to study the organization and dynamics of the Mediator coactivator and RNA polymerase II (Pol II) directly. Mediator and Pol II each form small transient and large stable clusters in living embryonic stem cells. Mediator and Pol II are colocalized in the stable clusters, which associate with chromatin, have properties of phase-separated condensates, and are sensitive to transcriptional inhibitors...
June 21, 2018: Science
Sadhan Das, Marpadga A Reddy, Parijat Senapati, Kenneth Stapleton, Linda Lanting, Mei Wang, Vishnu Amaram, Rituparna Ganguly, Lingxiao Zhang, Sridevi Devaraj, Dustin E Schones, Rama Natarajan
OBJECTIVE: Macrophages play key roles in inflammation and diabetic vascular complications. Emerging evidence implicates long noncoding RNAs in inflammation, but their role in macrophage dysfunction associated with inflammatory diabetic complications is unclear and was therefore investigated in this study. APPROACH AND RESULTS: RNA-sequencing and real-time quantitative PCR demonstrated that a long noncoding RNA Dnm3os (dynamin 3 opposite strand) is upregulated in bone marrow-derived macrophages from type 2 diabetic db/db mice, diet-induced insulin-resistant mice, and diabetic ApoE-/ - mice, as well as in monocytes from type 2 diabetic patients relative to controls...
June 21, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Saadia Khilji, Munerah Hamed, Jihong Chen, Qiao Li
Molecular regulation of stem cell differentiation is exerted through both genetic and epigenetic determinants over distal regulatory or enhancer regions. Understanding the mechanistic action of active or poised enhancers is therefore imperative for control of stem cell differentiation. Based on the genome-wide co-occurrence of different epigenetic marks in committed proliferating myoblasts, we have previously generated a 14-state chromatin state model to profile rexinoid-responsive histone acetylation in early myoblast differentiation...
June 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Pearl Chang, Yu-Fang Tseng, Pao-Yang Chen, Chung-Ju Rachel Wang
Meiosis is essential during sexual reproduction to generate haploid gametes. Genomic or epigenomic studies of meiosis in multicellular organisms using next-generation sequencing (NGS) methods have been limited because of the difficulty of collecting thousands to millions of meiocytes. Here, we describe a simple protocol to efficiently isolate maize male meiocytes from formaldehyde-fixed samples for NGS techniques that require chemical crosslinking to preserve complex interactions or chromatin architecture. Anthers at desired meiotic stages are selected, fixed with paraformaldehyde, and disrupted using a homogenizer...
June 2018: Current Protocols in Plant Biology
Xin Liu, Yuannyu Zhang, Yong Chen, Mushan Li, Zhen Shao, Michael Q Zhang, Jian Xu
Cis-regulatory elements (CREs) play a pivotal role in spatiotemporal control of tissue-specific gene expression, yet the molecular composition of the vast majority of CREs in native chromatin remains unknown. In this article, we describe the clustered regularly interspaced short palindromic repeats (CRISPR) affinity purification in situ of regulatory elements (CAPTURE) approach to simultaneously identify locus-specific chromatin-regulating protein complexes and long-range DNA interactions. Using an in vivo biotinylated nuclease-deficient Cas9 (dCas9) protein and programmable single guide RNAs (sgRNAs), this approach allows for high-resolution and locus-specific isolation of protein complexes and long-range chromatin looping associated with single copy CREs in mammalian cells...
June 19, 2018: Current Protocols in Molecular Biology
Ruby Yu, Xiaoyi Wang, Danesh Moazed
Histone post-translational modifications (PTMs) are associated with epigenetic states that form the basis for cell-type-specific gene expression1,2 . Once established, histone PTMs can be maintained by positive feedback involving enzymes that recognize a pre-existing histone modification and catalyse the same modification on newly deposited histones. Recent studies suggest that in wild-type cells, histone PTM-based positive feedback is too weak to mediate epigenetic inheritance in the absence of other inputs3-7 ...
June 20, 2018: Nature
Jin-Man Kim, Yonghwan Shin, Sunyoung Lee, Mi Yeong Kim, Vasu Punj, Hong-In Shin, Kyunghwan Kim, Jung-Min Koh, Daewon Jeong, Woojin An
Osteoclasts are multinuclear bone-resorbing cells that differentiate from hematopoietic precursor cells. Prostate cancer cells frequently spread to bone and secrete soluble signaling factors to accelerate osteoclast differentiation and bone resorption. However, processes and mechanisms that govern the expression of osteoclastogenic soluble factors secreted by prostate cancer cells are largely unknown. MacroH2A (mH2A) is a histone variant that replaces canonical H2A at designated genomic loci and establishes functionally distinct chromatin regions...
June 20, 2018: Oncogene
José L Neira, María Belén López, Paz Sevilla, Bruno Rizzuti, Ana Cámara-Artigas, Miguel Vidal, Juan L Iovanna
NUPR1 is a protumoral multifunctional intrinsically disordered protein (IDP), which is activated during the acute phases of pancreatitis. It interacts with other IDPs such as prothymosin α, as well as with folded proteins such as the C-terminal region of RING1-B (C-RING1B) of the Polycomb complex; in all those interactions, residues around Ala33 and Thr68 (the "hot-spot" region) of NUPR1 intervene. Its paralogue, NUPR1L, is also expressed in response to DNA-damage, it is p53-regulated, and its expression down-regulates that of the NUPR1 gene...
June 20, 2018: Biochemical Journal
Eva Bártová, Soňa Legartová, Jana Krejčí, Petra Řezníčková, Alena Svobodová Kovaříková, Jana Suchánková, Radek Fedr, Evgeny Smirnov, Matúš Hornáček, Ivan Raška
We studied how deficiency in lamins A/C and lamina-associated polypeptide 2α (Lap2α) affects DNA repair after irradiation. A-type lamins and Lap2α were not recruited to local DNA lesions and did not accumulate to γ-irradiation-induced foci (IRIF), as it is generally observed for well-known marker of DNA lesions, 53BP1 protein. At micro-irradiated chromatin of lmna double knockout (dn) and Lap2α dn cells, 53BP1 protein levels were reduced, compared to locally irradiated wild-type counterpart. Decreased levels of 53BP1 we also observed in whole populations of lmna dn and Lap2α dn cells, irradiated by UV light...
June 19, 2018: Journal of Cellular Biochemistry
Nikita Deshpande, Victoria H Meller
Many heterogametic organisms adjust sex chromosome expression to accommodate differences in gene dosage. This requires selective recruitment of regulatory factors to the modulated chromosome. How these factors are localized to a chromosome with requisite accuracy is poorly understood. Drosophila melanogaster males increase expression from their single X chromosome. Identification of this chromosome involves cooperation between different classes of X-identity elements. The Chromatin Entry Sites (CES) recruit a chromatin-modifying complex that spreads into nearby genes and increases expression...
June 19, 2018: Genetics
Prashanth Krishna Shastrula, Peder J Lund, Benjamin A Garcia, Susan M Janicki
The histone H3 variant, H3.3, is a highly conserved and dynamic regulator of chromatin organization.  Therefore, fully elucidating its nucleosome incorporation mechanisms is essential to understanding its functions in epigenetic inheritance.  We previously identified the RNase P protein subunit, Rpp29, as a repressor of H3.3 chromatin assembly.  Here, we use a biochemical assay to show that Rpp29 interacts with H3.3 through a sequence element in its own N-terminus, and we identify a novel interaction with histone H2B at an adjacent site...
June 19, 2018: Journal of Biological Chemistry
Xiaowei Diao, Xiubin Chen, Yurui Pi, Yu Zhang, Fangfang Wang, Ping Liu, Yanhong Gao, Xiaojun Wang, Sijun Yang, Shan Lu
Erythropoietin‑producing hepatocellular carcinoma cell surface type‑A receptor 3 (EPHA3) has been found to promote the proliferation and survival of prostate cancer (PCa) cell lines and prostate tumor development in nude mice. However, the regulation of EPHA3 in PCa remains largely unknown. This study is aimed to investigate the association between EPHA3 expression and androgen receptor (AR) signaling and the potential mechanism. We determined mRNA and protein levels of EPHA3 and AR signaling‑related genes in the PCa cell line 22Rv1 by reverse transcription‑polymerase chain reaction (RT‑PCR) and western blotting, respectively...
June 18, 2018: Oncology Reports
James M Dunce, Orla M Dunne, Matthew Ratcliff, Claudia Millán, Suzanne Madgwick, Isabel Usón, Owen R Davies
Meiotic chromosomes adopt unique structures in which linear arrays of chromatin loops are bound together in homologous chromosome pairs by a supramolecular protein assembly, the synaptonemal complex. This three-dimensional scaffold provides the essential structural framework for genetic exchange by crossing over and subsequent homolog segregation. The core architecture of the synaptonemal complex is provided by SYCP1. Here we report the structure and self-assembly mechanism of human SYCP1 through X-ray crystallographic and biophysical studies...
June 18, 2018: Nature Structural & Molecular Biology
Yuan Gao, Haiyun Gan, Zhenkun Lou, Zhiguo Zhang
Bivalent chromatin domains containing repressive H3K27me3 and active H3K4me3 modifications are barriers for the expression of lineage-specific genes in ES cells and must be resolved for the transcription induction of these genes during differentiation, a process that remains largely unknown. Here, we show that Asf1a, a histone chaperone involved in nucleosome assembly and disassembly, regulates the resolution of bivalent domains and activation of lineage-specific genes during mouse ES cell differentiation. Deletion of Asf1a does not affect the silencing of pluripotent genes, but compromises the expression of lineage-specific genes during ES cell differentiation...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Nathan H Lazar, Kimberly A Nevonen, Brendan O'Connell, Christine McCann, Rachel J O'Neill, Richard E Green, Thomas J Meyer, Mariam Okhovat, Lucia Carbone
The relationship between evolutionary genome remodeling and the three-dimensional structure of the genome remain largely unexplored. Here, we use the heavily rearranged gibbon genome to examine how evolutionary chromosomal rearrangements impact genome-wide chromatin interactions, topologically associating domains (TADs), and their epigenetic landscape. We use high-resolution maps of gibbon-human breaks of synteny (BOS), apply Hi-C in gibbon, measure an array of epigenetic features, and perform cross-species comparisons...
June 18, 2018: Genome Research
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