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chromatin interaction

Jenna F DuMond, Xue Zhang, Yuichiro Izumi, Kevin Ramkissoon, Guanghui Wang, Marjan Gucek, Xujing Wang, Maurice B Burg, Joan D Ferraris
NFAT5 is a transcription factor originally identified because it is activated by hypertonicity and that activation increases expression of genes that protect against the adverse effects of the hypertonicity. However, its targets also include genes not obviously related to tonicity. The transactivating domain of NFAT5 is contained in its c-terminal region, which is predicted to be unstructured. Unstructured regions are common in transcription factors particularly in transactivating domains where they can bind co-regulatory proteins essential to their function...
October 7, 2016: Physiological Genomics
Jawed Iqbal, Mairaj Ahmed Ansari, Binod Kumar, Dipanjan Dutta, Arunava Roy, Leela Chikoti, Gina Pisano, Sujoy Dutta, Shahrooz Vahedi, Mohanan Valiya Veettil, Bala Chandran
IFI16 (gamma-interferon-inducible protein 16), a predominantly nuclear protein involved in transcriptional regulation, also functions as an innate immune response DNA sensor and induces the IL-1β and antiviral type-1 interferon-β (IFN-β) cytokines. We have shown that IFI16, in association with BRCA1, functions as a sequence independent nuclear sensor of episomal dsDNA genomes of KSHV, EBV and HSV-1. Recognition of these herpesvirus genomes resulted in IFI16 acetylation, BRCA1-IFI16-ASC-procaspase-1 inflammasome formation, cytoplasmic translocation, and IL-1β generation...
October 2016: PLoS Pathogens
Inderjeet Kaur, Mohammad Zeeshan, Ekta Saini, Abhinav Kaushik, Asif Mohmmed, Dinesh Gupta, Pawan Malhotra
Post-transcriptional and post-translational modifications play a major role in Plasmodium life cycle regulation. Lysine methylation of histone proteins is well documented in several organisms, however in recent years lysine methylation of proteins outside histone code is emerging out as an important post-translational modification (PTM). In the present study we have performed global analysis of lysine methylation of proteins in asexual blood stages of Plasmodium falciparum development. We immunoprecipitated stage specific Plasmodium lysates using anti-methyl lysine specific antibodies that immunostained the asexual blood stage parasites...
October 20, 2016: Scientific Reports
Darren M Hutt, Daniela Martino Roth, Christelle Marchal, Marion Bouchecareilh
Gene expression is regulated in part through the reversible acetylation of histones, by the action of histone acetyltransferases (HAT) and histone deacetylases (HDAC). HAT activity results in the addition of acetyl groups on the lysine residues of histone tails leading to decondensation of the chromatin, and increased gene transcription in general, whereas HDACs remove these acetyl groups, thus leading to an overall suppression of gene transcription. Recent evidence has elucidated that histones are not the only components of the proteome that are targeted by HATs and HDACs...
2017: Methods in Molecular Biology
Chun Ma, Violetta Karwacki-Neisius, Haoran Tang, Wenjing Li, Zhennan Shi, Haolin Hu, Wenqi Xu, Zhentian Wang, Lingchun Kong, Ruitu Lv, Zheng Fan, Wenhao Zhou, Pengyuan Yang, Feizhen Wu, Jianbo Diao, Li Tan, Yujiang Geno Shi, Fei Lan, Yang Shi
Nono is a component of the para-speckle, which stores and processes RNA. Mouse embryonic stem cells (mESCs) lack para-speckles, leaving the function of Nono in mESCs unclear. Here, we find that Nono functions as a chromatin regulator cooperating with Erk to regulate mESC pluripotency. We report that Nono loss results in robust self-renewing mESCs with epigenomic and transcriptomic features resembling the 2i (GSK and Erk inhibitors)-induced "ground state." Erk interacts with and is required for Nono localization to a subset of bivalent genes that have high levels of poised RNA polymerase...
October 18, 2016: Cell Reports
Hyejung Won, Luis de la Torre-Ubieta, Jason L Stein, Neelroop N Parikshak, Jerry Huang, Carli K Opland, Michael J Gandal, Gavin J Sutton, Farhad Hormozdiari, Daning Lu, Changhoon Lee, Eleazar Eskin, Irina Voineagu, Jason Ernst, Daniel H Geschwind
Three-dimensional physical interactions within chromosomes dynamically regulate gene expression in a tissue-specific manner. However, the 3D organization of chromosomes during human brain development and its role in regulating gene networks dysregulated in neurodevelopmental disorders, such as autism or schizophrenia, are unknown. Here we generate high-resolution 3D maps of chromatin contacts during human corticogenesis, permitting large-scale annotation of previously uncharacterized regulatory relationships relevant to the evolution of human cognition and disease...
October 19, 2016: Nature
Maria Böhm, Marco Wachtel, Joana G Marques, Natalie Streiff, Dominik Laubscher, Paolo Nanni, Kamel Mamchaoui, Raffaella Santoro, Beat W Schäfer
A vast number of cancer genes are transcription factors that drive tumorigenesis as oncogenic fusion proteins. Although the direct targeting of transcription factors remains challenging, therapies aimed at oncogenic fusion proteins are attractive as potential treatments for cancer. There is particular interest in targeting the oncogenic PAX3-FOXO1 fusion transcription factor, which induces alveolar rhabdomyosarcoma (aRMS), an aggressive cancer of skeletal muscle cells for which patient outcomes remain dismal...
October 17, 2016: Journal of Clinical Investigation
Buki Kwon, Palinda Ruvan Munashingha, Yong-Keol Shin, Chul-Hwan Lee, Bing Li, Yeon-Soo Seo
Highly conserved eukaryotic histones are polybasic proteins that package DNA into nucleosomes, a building block of chromatin, allowing extremely long DNA molecules to form compact and discrete chromosomes. The histone N-terminal tails that extend from the nucleosome core act as docking sites for many proteins through diverse posttranslational modifications, regulating various DNA transactions. In this report, we present evidence that the nucleosomes can positively regulate the enzymatic activity of Rad27 (yeast Fen1), a major processing enzyme important for Okazaki fragment in eukaryotes...
October 19, 2016: FEBS Journal
Xiang Du, Mi-Die Xu, Yiqin Wang, Wei-Wei Weng, Ping Wei, Peng Qi, Qiongyan Zhang, Cong Tan, Shujuan Ni, Lei Dong, Yusi Yang, Wanrun Lin, Qinghua Xu, Dan Huang, Zhaohui Huang, Yuqing Ma, Wei Zhang, Weiqi Sheng
PURPOSE: The long noncoding RNA (lncRNA) PVT1 is an important epigenetic regulator with a critical role in human tumors. Here, we aimed to investigate the clinical application and the potential molecular mechanisms of PVT1 in gastric cancer (GC) tumorigenesis and progression. EXPERIMENTAL DESIGN: The expression level of PVT1 was determined by RT-qPCR analysis in 190 pairs of GC tissues and adjacent normal gastric mucosa tissues (ANTs). The biological functions of PVT1 were assessed by in vitro and in vivo functional experiments...
October 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Vasily M Studitsky, Ekaterina V Nizovtseva, Alexey K Shaytan, Donal S Luse
Packaging of DNA into chromatin affects all processes on DNA. Nucleosomes present a strong barrier to transcription, raising important questions about the nature and the mechanisms of overcoming the barrier. Recently it was shown that DNA sequence, DNA-histone interactions and backtracking by RNA polymerase II (Pol II) all contribute to formation of the barrier. After partial uncoiling of nucleosomal DNA from histone octamer by Pol II and backtracking of the enzyme, nucleosomal DNA recoils on the octamer, locking Pol II in the arrested state...
2016: Biochemistry & Molecular Biology Journal
Fu Liang Ng, Ebbe Boedtkjer, Shu Ye, Mark Caulfield
OBJECTIVE: Chromosome 3p24.1 containing the SLC4A7 gene has been identified by genome-wide association studies as one of the genomic loci that influence blood pressure. SLC4A7 encodes electroneutral Na/HCO3 co-transporter (NBCn1) which regulates intracellular pH (pHi) in various tissues including vascular smooth muscle and endothelium, with knockout models demonstrating an altered blood pressure phenotype. We conducted a functional study of blood pressure-associated single nucleotide polymorphisms at the SLC4A7 locus in primary cultures of human vascular smooth muscle and endothelial cells...
September 2016: Journal of Hypertension
Peter F Davies, Elisabetta Manduchi, Christian J Stoeckert, Yi-Zhou Jiang
Hemodynamics creates a constantly changing physical and chemical environment to which the arterial endothelium is exquisitely sensitive. Biomechanical stresses are intrinsic to blood flow characteristics and blood pressure and therefore are important considerations in hypertension. Near branching anatomical sites in arteries, blood flow separates from the main flow to undergo complex multi-directional characteristics for a part of each cardiac cycle (collectively referred to as disturbed flow). Atherosclerosis and aneurysmal pathology develop preferentially at disturbed flow locations, particularly when an additional cardiovascular risk factor such as hypercholesterolemia or high blood pressure are present...
September 2016: Journal of Hypertension
Deepesh Pandey, Daijiro Tori, Yohei Nomura, Dan Berkowitz, Lewis Romer
OBJECTIVE: Kruppel Like Factor 15 (KLF15) has recently been shown to be critical for activation of proinflammatory processes in vascular smooth muscle and atherogenesis. Although KLF15 is abundantly expressed in vascular endothelium there is a significant lack of knowledge regarding the role of KLF15 in the regulation of vascular endothelial function. Here we tested the hypothesis that KLF15 is a critical regulator of Arg2 transcription in hypoxia exposed human pulmonary microvascular endothelial cells (HPMEC) and that it plays critical role in pathogenesis of pulmonary hypertension (PHTN)...
September 2016: Journal of Hypertension
Stephen Harrap
Genetic discovery in blood pressure is generally referenced in relation to protein-coding genes, despite the fact that genes less than 2% of the genome. Recent exploration of the DNA sequences between genes, once called "junk" DNA, has revealed a wealth of transcripts for RNA species that do not encode protein. These non-coding RNAs (ncRNAs) have emerged as dynamic managers of the business of the genome, able to coordinate the expression of genes in time and space to achieve the complexities of normal development and growth...
September 2016: Journal of Hypertension
Yoo-Sun Kim, Eunju Kim, Yoon Jung Park, Yuri Kim
Neuroblastoma (NB) is childhood malignancy that retains characteristics of cancer stem cells (CSCs). Targeting the CSCs is one of the therapeutic strategies proposed to achieve complete remission of NB. β-carotene (BC), an active precursor of retinoids, is a well-known antioxidant reported to possess anti-CSCs effects. Here, we investigated the involvement of retinoic acid receptors (RARs) in the anti-CSCs effects of BC. Treatment with BC or retinoic acid (RA) upregulated RARβ mRNA expression in two NB cell lines...
October 14, 2016: Biochemical and Biophysical Research Communications
M Gokulnath, R Swetha, G Thejaswini, P Shilpa, N Selvamurugan
Transforming growth factor-beta1 (TGF-β1) plays a significant role in breast cancer mediated bone metastasis, and it stimulated expression of matrix metalloproteinase-13 (MMP-13; an invasive and metastasis gene) via activating transcription factor-3 (ATF-3) in human breast cancer cells (MDA-MB231). We further dissected the role of ATF-3 and its interacting proteins (activator protein-1; AP-1) for TGF-β1-stimulation of MMP-13 expression in these cells. Chromatin immunoprecipitation (ChIP) experiment identified the TGF-β1-stimulation of ATF-3 interaction at the AP-1 site of the MMP-13 promoter in a sustained and prolonged manner in MDA-MB231 cells...
October 14, 2016: International Journal of Biological Macromolecules
Saeed Izadi, Ramu Anandakrishnan, Alexey V Onufriev
Molecular Dynamics (MD) simulations based on the implicit solvent generalized Born (GB) models can provide significant computational advantages over the traditional explicit solvent simulations. However, the standard GB becomes prohibitively expensive for all-atom simulations of large structures; the model scales poorly, ~n^2, with the number of solute atoms. Here we combine our recently developed Optimal Point Charge Approximation (OPCA) with the Hierarchical Charge Partitioning (HCP) approximation to present an ~n log n multi-scale, yet fully atomistic, GB model (GB-HCPO)...
October 17, 2016: Journal of Chemical Theory and Computation
Jean-François Millau, Patrick Wijchers, Luc Gaudreau
A regulatory program involving hundreds of genes is coordinated by p53 to prevent carcinogenesis in response to stress. Given the importance of chromatin loops in gene regulation, we investigated whether DNA interactions participate in the p53 stress response. To shed light on this issue, we measured the binding dynamics of cohesin in response to stress. We reveal that cohesin is remodeled at specific loci during the stress response and that its binding within genes negatively correlates with transcription...
2016: PloS One
Samuel Corless, Nick Gilbert
Disruptions in chromatin structure are necessary for the regulation of eukaryotic genomes, from remodelling of nucleosomes at the base pair level through to large-scale chromatin domains that are hundreds of kilobases in size. RNA polymerase is a powerful motor which, prevented from turning with the tight helical pitch of the DNA, generates over-wound DNA ahead of itself and under-wound DNA behind. Mounting evidence supports a central role for transcription-dependent DNA supercoiling in disrupting chromatin structure at all scales...
2016: Biophysical Reviews
Takamasa Hirano, Hidetoshi Hasuwa, Haruhiko Siomi
The mouse testis has served as a popular model system to study a wide range of biological processes, including germ cell development, meiosis, epigenetic changes of chromatin, transposon silencing, and small RNA-mediated epigenetic modifications. PIWI-interacting RNAs (piRNAs) are a class of small RNAs that are almost exclusively expressed in animal gonads. They repress transposons by forming effector complexes with PIWI proteins to maintain genome integrity of the germline. Here we describe detailed procedures of how to produce monoclonal antibodies against a mouse nuclear PIWI protein, MIWI2, which functions in de novo DNA methylation of target transposon loci...
2017: Methods in Molecular Biology
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