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Chromatin structure regulation

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https://www.readbyqxmd.com/read/28549174/phosphorylated-sirt1-associates-with-replication-origins-to-prevent-excess-replication-initiation-and-preserve-genomic-stability
#1
Koichi Utani, Haiqing Fu, Sang-Min Jang, Anna B Marks, Owen K Smith, Ya Zhang, Christophe E Redon, Noriaki Shimizu, Mirit I Aladjem
Chromatin structure affects DNA replication patterns, but the role of specific chromatin modifiers in regulating the replication process is yet unclear. We report that phosphorylation of the human SIRT1 deacetylase on Threonine 530 (T530-pSIRT1) modulates DNA synthesis. T530-pSIRT1 associates with replication origins and inhibits replication from a group of 'dormant' potential replication origins, which initiate replication only when cells are subject to replication stress. Although both active and dormant origins bind T530-pSIRT1, active origins are distinguished from dormant origins by their unique association with an open chromatin mark, histone H3 methylated on lysine 4...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28542146/the-role-of-extracellular-histone-in-organ-injury
#2
REVIEW
Eleanor Silk, Hailin Zhao, Hao Weng, Daqing Ma
Histones are intra-nuclear cationic proteins that are present in all eukaryotic cells and are highly conserved across species. Within the nucleus, they provide structural stability to chromatin and regulate gene expression. Histone may be released into the extracellular space in three forms: freely, as a DNA-bound nucleosome or as part of neutrophil extracellular traps, and all three can be detected in serum after significant cellular death such as sepsis, trauma, ischaemia/reperfusion injury and autoimmune disease...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28539972/site-specific-regulation-of-histone-h1-phosphorylation-in-pluripotent-cell-differentiation
#3
Ruiqi Liao, Craig A Mizzen
BACKGROUND: Structural variation among histone H1 variants confers distinct modes of chromatin binding that are important for differential regulation of chromatin condensation, gene expression and other processes. Changes in the expression and genomic distributions of H1 variants during cell differentiation appear to contribute to phenotypic differences between cell types, but few details are known about the roles of individual H1 variants and the significance of their disparate capacities for phosphorylation...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28533432/the-atp-dependent-chromatin-remodeling-enzymes-chd6-chd7-and-chd8-exhibit-distinct-nucleosome-binding-and-remodeling-activities
#4
Benjamin J Manning, Timur Yusufzai
Proper chromatin regulation is central to genome function and maintenance. The group III CHD family of ATP-dependent chromatin remodeling enzymes--comprising CHD6, CHD7, CHD8, and CHD9--has well-documented roles in transcription regulation impacting both organism development and disease etiology. These four enzymes are similar in their constituent domains, yet these enzymes fill surprisingly non-redundant roles in the cell, with deficiencies in individual enzymes leading to dissimilar disease states such as CHARGE syndrome or autism spectrum disorders...
May 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28530531/the-complexity-of-dek-signaling-in-cancer-progression
#5
Yong Teng, Liwei Lang, Catherine E Jauregui
The DNA binding protein and chromatin structural regulator DEK regulates many cellular processes. These include proliferation, differentiation, apoptosis, senescence, DNA repairing and the maintenance of stem cell phenotype. DEK is increasingly recognized as a crucial player in many steps of cancer initiation and progression, and is precisely regulated by abundant promoting and inhibiting factors directly or indirectly. DEK may serve as an architectural modulating protein to regulate the expression and function of multiple human genes in cancer cells...
May 21, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28529337/dynamic-chromatin-technologies-from-individual-molecules-to-epigenomic-regulation-in-cells
#6
REVIEW
Olivier Cuvier, Beat Fierz
The establishment and maintenance of chromatin states involves multiscale dynamic processes integrating transcription factor and multiprotein effector dynamics, cycles of chemical chromatin modifications, and chromatin structural organization. Recent developments in genomic technologies are emerging that are enabling a view beyond ensemble- and time-averaged properties and are revealing the importance of dynamic chromatin states for cell fate decisions, differentiation and reprogramming at the single-cell level...
May 22, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28526340/unfolding-the-pathogenesis-of-scleroderma-through-genomics-and-epigenomics
#7
REVIEW
Pei-Suen Tsou, Amr H Sawalha
With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while genetic susceptibility to SSc appears to be modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated...
May 16, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28525758/targeted-degradation-of-ctcf-decouples-local-insulation-of-chromosome-domains-from-genomic-compartmentalization
#8
Elphège P Nora, Anton Goloborodko, Anne-Laure Valton, Johan H Gibcus, Alec Uebersohn, Nezar Abdennur, Job Dekker, Leonid A Mirny, Benoit G Bruneau
The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28521327/epigenomics-pharmacoepigenomics-and-personalized-medicine-in-cervical-cancer
#9
Shama Prasada Kabekkodu, Sanjiban Chakrabarty, Supriti Ghosh, Angela Brand, Kapaettu Satyamoorthy
Epigenomics encompasses the study of genome-wide changes in DNA methylation, histone modifications and noncoding RNAs leading to altered transcription, chromatin structure, and posttranscription RNA processing, respectively, resulting in an altered rate of gene expression. The role of epigenetic modifications facilitating human diseases is well established. Previous studies have identified histone and cytosine code during normal and pathological conditions with special emphasis on how these modifications regulate transcriptional events...
May 19, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28511927/coordinated-regulation-of-ifitm1-2-and-3-genes-by-an-ifn-responsive-enhancer-through-long-range-chromatin-interactions
#10
Ping Li, Ming-Lei Shi, Wen-Long Shen, Zhang Zhang, De-Jian Xie, Xiang-Yuan Zhang, Chao He, Yan Zhang, Zhi-Hu Zhao
Interferon-induced transmembrane protein (IFITM) 1, 2 and 3 are a family of interferon (IFN)-induced transmembrane proteins that block entry of a broad spectrum of pathogens. However, the transcriptional regulation of these genes, especially whether there exists any enhancers and their roles during the IFN induction process remain elusive. Here, combining episomal luciferase reporter assay and in vivo genome editing, we identified an IFNβ-responsive enhancer located 35kb upstream of IFITM3 gene promoter upregulating the IFNβ-induced expression of IFITM1, 2 and 3 genes, thus contributing to IFNβ-mediated resistance to influenza A virus (IAV) infection...
May 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28511652/ing3-promotes-prostate-cancer-growth-by-activating-the-androgen-receptor
#11
Arash Nabbi, Urszula L McClurg, Subhash Thalappilly, Amal Almami, Mahsa Mobahat, Tarek A Bismar, Olivier Binda, Karl T Riabowol
BACKGROUND: The androgen receptor (AR) is a major driver of prostate cancer, and increased AR levels and co-activators of the receptor promote the development of prostate cancer. INhibitor of Growth (ING) proteins target lysine acetyltransferase or lysine deacetylase complexes to the histone H3K4Me3 mark of active transcription, to affect chromatin structure and gene expression. ING3 is a stoichiometric member of the TIP60 lysine acetyltransferase complex implicated in prostate cancer development...
May 16, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28510225/controlling-gene-expression-by-dna-mechanics-emerging-insights-and-challenges
#12
REVIEW
David Levens, Laura Baranello, Fedor Kouzine
Transcription initiation is a major control point for the precise regulation of gene expression. Our knowledge of this process has been mainly derived from protein-centric studies wherein cis-regulatory DNA sequences play a passive role, mainly in arranging the protein machinery to coalesce at the transcription start sites of genes in a spatial and temporal-specific manner. However, this is a highly dynamic process in which molecular motors such as RNA polymerase II (RNAPII), helicases, and other transcription factors, alter the level of mechanical force in DNA, rather than simply a set of static DNA-protein interactions...
September 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28510218/controlling-gene-expression-by-dna-mechanics-emerging-insights-and-challenges
#13
REVIEW
David Levens, Laura Baranello, Fedor Kouzine
Transcription initiation is a major control point for the precise regulation of gene expression. Our knowledge of this process has been mainly derived from protein-centric studies wherein cis-regulatory DNA sequences play a passive role, mainly in arranging the protein machinery to coalesce at the transcription start sites of genes in a spatial and temporal-specific manner. However, this is a highly dynamic process in which molecular motors such as RNA polymerase II (RNAPII), helicases, and other transcription factors, alter the level of mechanical force in DNA, rather than simply a set of static DNA-protein interactions...
November 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28507058/hepatocyte-nuclear-factor-1%C3%AE-regulates-urinary-concentration-and-response-to-hypertonicity
#14
Karam Aboudehen, Lama Noureddine, Patricia Cobo-Stark, Svetlana Avdulov, Shayan Farahani, Micah D Gearhart, Daniel G Bichet, Marco Pontoglio, Vishal Patel, Peter Igarashi
The transcription factor hepatocyte nuclear factor-1β (HNF-1β) is essential for normal kidney development and function. Inactivation of HNF-1β in mouse kidney tubules leads to early-onset cyst formation and postnatal lethality. Here, we used Pkhd1/Cre mice to delete HNF-1β specifically in renal collecting ducts (CDs). CD-specific HNF-1β mutant mice survived long term and developed slowly progressive cystic kidney disease, renal fibrosis, and hydronephrosis. Compared with wild-type littermates, HNF-1β mutant mice exhibited polyuria and polydipsia...
May 15, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28506839/evolutionary-relationships-among-protein-lysine-deacetylases-of-parasites-causing-neglected-diseases
#15
Larissa L S Scholte, Marina M Mourão, Fabiano Sviatopolk-Mirsky Pais, Jelena Melesina, Dina Robaa, Angela C Volpini, Wolfgang Sippl, Raymond J Pierce, Guilherme Oliveira, Laila A Nahum
The availability of the genomic data of diverse parasites provides an opportunity to identify new drug candidates against neglected tropical diseases affecting people worldwide. Histone modifying enzymes (HMEs) are potential candidates since they play key roles in the regulation of chromatin modifications, thus globally regulating gene expression. Furthermore, aberrant epigenetic states are often associated with human diseases, leading to great interest in HMEs as therapeutic targets. Our work focused on two families of protein lysine deacetylases (HDACs and sirtuins)...
May 13, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28505071/myc-master-regulator-of-the-cancer-epigenome-and-transcriptome
#16
REVIEW
Candace J Poole, Jan van Riggelen
Overexpression of MYC is a hallmark of many human cancers. The MYC oncogene has long been thought to execute its neoplastic functions by acting as a classic transcription factor, deregulating the expression of a large number of specific target genes. However, MYC's influence on many of these target genes is rather modest and there is little overlap between MYC regulated genes in different cell types, leaving many mechanistic questions unanswered. Recent advances in the field challenge the dogma further, revealing a role for MYC that extends beyond the traditional concept of a sequence-specific transcription factor...
May 13, 2017: Genes
https://www.readbyqxmd.com/read/28504305/intranuclear-and-higher-order-chromatin-organization-of-the-major-histone-gene-cluster-in-breast-cancer
#17
Andrew J Fritz, Prachi N Ghule, Joseph R Boyd, Coralee E Tye, Natalie A Page, Deli Hong, Adam S Weinheimer, A Rasim Barutcu, Diana L Gerrard, Seth Frietze, Sayyed K Zaidi, Anthony Imbalzano, Jane B Lian, Janet L Stein, Gary S Stein
Alterations in nuclear morphology are common in cancer progression. However, the degree to which gross morphological abnormalities translate into compromised higher-order chromatin organization is poorly understood. To explore the functional links between gene expression and chromatin structure in breast cancer, we performed RNA-seq gene expression analysis on the basal breast cancer progression model based on human MCF10A cells. Positional gene enrichment identified the major histone gene cluster at chromosome 6p22 as one of the most significantly upregulated (and not amplified) clusters of genes from the normal-like MCF10A to premalignant MCF10AT1 and metastatic MCF10CA1a cells...
May 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28503382/poly-adp-ribosylation-is-present-in-murine-sciatic-nerve-fibers-and-is-altered-in-a-charcot-marie-tooth-1e-neurodegenerative-model
#18
Laura I Lafon Hughes, Carlos J Romeo Cardeillac, Karina B Cal Castillo, Salomé C Vilchez Larrea, José R Sotelo Sosa, Gustavo A Folle Ungo, Silvia H Fernández Villamil, Alejandra E Kun González
BACKGROUND: Poly-ADP-ribose (PAR) is a polymer synthesized by poly-ADP-ribose polymerases (PARPs) as a postranslational protein modification and catabolized mainly by poly-ADP-ribose glycohydrolase (PARG). In spite of the existence of cytoplasmic PARPs and PARG, research has been focused on nuclear PARPs and PAR, demonstrating roles in the maintenance of chromatin architecture and the participation in DNA damage responses and transcriptional regulation. We have recently detected non-nuclear PAR structurally and functionally associated to the E-cadherin rich zonula adherens and the actin cytoskeleton of VERO epithelial cells...
2017: PeerJ
https://www.readbyqxmd.com/read/28501329/eukaryotic-dna-replication-orchestrated-action-of-multi-subunit-protein-complexes
#19
REVIEW
Sukhyun Kang, Mi-Sun Kang, Eunjin Ryu, Kyungjae Myung
Genome duplication is an essential process to preserve genetic information between generations. The eukaryotic cell cycle is composed of functionally distinct phases: G1, S, G2, and M. One of the key replicative proteins that participate at every stage of DNA replication is the Mcm2-7 complex, a replicative helicase. In the G1 phase, inactive Mcm2-7 complexes are loaded on the replication origins by replication-initiator proteins, ORC and Cdc6. Two kinases, S-CDK and DDK, convert the inactive origin-loaded Mcm2-7 complex to an active helicase, the CMG complex in the S phase...
May 1, 2017: Mutation Research
https://www.readbyqxmd.com/read/28498870/brg1-chromatin-remodeling-atpase-balances-germ-layer-patterning-by-amplifying-the-transcriptional-burst-at-midblastula-transition
#20
Gabriele Wagner, Nishant Singhal, Dario Nicetto, Tobias Straub, Elisabeth Kremmer, Ralph A W Rupp
Zygotic gene expression programs control cell differentiation in vertebrate development. In Xenopus, these programs are initiated by local induction of regulatory genes through maternal signaling activities in the wake of zygotic genome activation (ZGA) at the midblastula transition (MBT). These programs lay down the vertebrate body plan through gastrulation and neurulation, and are accompanied by massive changes in chromatin structure, which increasingly constrain cellular plasticity. Here we report on developmental functions for Brahma related gene 1 (Brg1), a key component of embyronic SWI/SNF chromatin remodeling complexes...
May 2017: PLoS Genetics
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