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https://www.readbyqxmd.com/read/28428255/nucleosome-nucleosome-interactions-via-histone-tails-and-linker-dna-regulate-nuclear-rigidity
#1
Yuta Shimamoto, Sachiko Tamura, Hiroshi Masumoto, Kazuhiro Maeshima
Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We addressed this in the present study by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28424523/cohesin-is-positioned-in-mammalian-genomes-by-transcription-ctcf-and-wapl
#2
Georg A Busslinger, Roman R Stocsits, Petra van der Lelij, Elin Axelsson, Antonio Tedeschi, Niels Galjart, Jan-Michael Peters
Mammalian genomes are spatially organized by CCCTC-binding factor (CTCF) and cohesin into chromatin loops and topologically associated domains, which have important roles in gene regulation and recombination. By binding to specific sequences, CTCF defines contact points for cohesin-mediated long-range chromosomal cis-interactions. Cohesin is also present at these sites, but has been proposed to be loaded onto DNA elsewhere and to extrude chromatin loops until it encounters CTCF bound to DNA. How cohesin is recruited to CTCF sites, according to this or other models, is unknown...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28424352/chromatin-module-inference-on-cellular-trajectories-identifies-key-transition-points-and-poised-epigenetic-states-in-diverse-developmental-processes
#3
Sushmita Roy, Rupa Sridharan
Changes in chromatin state play important roles in cell fate transitions. Current computational approaches to analyze chromatin modifications across multiple cell types do not model how the cell types are related on a lineage or over time. To overcome this limitation, we have developed a method called CMINT (Chromatin Module INference on Trees), a probabilistic clustering approach to systematically capture chromatin state dynamics across multiple cell types. Compared to existing approaches, CMINT can handle complex lineage topologies, capture higher quality clusters, and reliably detect chromatin transitions between cell types...
April 19, 2017: Genome Research
https://www.readbyqxmd.com/read/28413449/links-between-dna-methylation-and-nucleosome-occupancy-in-the-human-genome
#4
Clayton K Collings, John N Anderson
BACKGROUND: DNA methylation is an epigenetic modification that is enriched in heterochromatin but depleted at active promoters and enhancers. However, the debate on whether or not DNA methylation is a reliable indicator of high nucleosome occupancy has not been settled. For example, the methylation levels of DNA flanking CTCF sites are higher in linker DNA than in nucleosomal DNA, while other studies have shown that the nucleosome core is the preferred site of methylation. In this study, we make progress toward understanding these conflicting phenomena by implementing a bioinformatics approach that combines MNase-seq and NOMe-seq data and by comprehensively profiling DNA methylation and nucleosome occupancy throughout the human genome...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28408976/when-tads-go-bad-chromatin-structure-and-nuclear-organisation-in-human-disease
#5
REVIEW
Vera B Kaiser, Colin A Semple
Chromatin in the interphase nucleus is organised as a hierarchical series of structural domains, including self-interacting domains called topologically associating domains (TADs). This arrangement is thought to bring enhancers into closer physical proximity with their target genes, which often are located hundreds of kilobases away in linear genomic distance. TADs are demarcated by boundary regions bound by architectural proteins, such as CTCF and cohesin, although much remains to be discovered about the structure and function of these domains...
2017: F1000Research
https://www.readbyqxmd.com/read/28406749/nucleosome-repositioning-during-differentiation-of-a-human-myeloid-leukemia-cell-line
#6
Vladimir B Teif, Jan-Philipp Mallm, Tanvi Sharma, David B Mark Welch, Karsten Rippe, Roland Eils, Jörg Langowski, Ada L Olins, Donald E Olins
Cell differentiation is associated with changes in chromatin organization and gene expression. In this study, we examine chromatin structure following differentiation of the human myeloid leukemia cell line (HL-60/S4) into granulocytes with retinoic acid (RA) or into macrophage with phorbol ester (TPA). We performed ChIP-seq of histone H3 and its modifications, analyzing changes in nucleosome occupancy, nucleosome repeat length, eu-/heterochromatin redistribution and properties of epichromatin (surface chromatin adjacent to the nuclear envelope)...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28388437/the-bet-protein-brd2-cooperates-with-ctcf-to-enforce-transcriptional-and-architectural-boundaries
#7
Sarah C Hsu, Thomas G Gilgenast, Caroline R Bartman, Christopher R Edwards, Aaron J Stonestrom, Peng Huang, Daniel J Emerson, Perry Evans, Michael T Werner, Cheryl A Keller, Belinda Giardine, Ross C Hardison, Arjun Raj, Jennifer E Phillips-Cremins, Gerd A Blobel
Bromodomain and extraterminal motif (BET) proteins are pharmacologic targets for the treatment of diverse diseases, yet the roles of individual BET family members remain unclear. We find that BRD2, but not BRD4, co-localizes with the architectural/insulator protein CCCTC-binding factor (CTCF) genome-wide. CTCF recruits BRD2 to co-bound sites whereas BRD2 is dispensable for CTCF occupancy. Disruption of a CTCF/BRD2-occupied element positioned between two unrelated genes enables regulatory influence to spread from one gene to another, suggesting that CTCF and BRD2 form a transcriptional boundary...
April 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28373182/energy-balance-modulation-impacts-epigenetic-reprogramming-er%C3%AE-and-er%C3%AE-expression-and-mammary-tumor-development-in-mmtv-neu-transgenic-mice
#8
Emily L Rossi, Sarah M Dunlap, Laura W Bowers, Subreen A Khatib, Steven S Doerstling, Laura A Smith, Manu A Sharma, Darcy Holley, Powel H Brown, Marcos R Estecio, Donna F Kusewitt, Linda A deGraffenried, Scott J Bultman, Stephen D Hursting
The association between obesity and breast cancer risk and prognosis is well established in ER-positive disease but less clear in HER2-positive disease. Here, we report preclinical evidence suggesting weight maintenance through calorie restriction may limit risk of HER2-positive breast cancer. In female MMTV-HER2/neu transgenic mice, we found that ERα and ERβ expression, mammary tumorigenesis and survival are energy balance-dependent in association with epigenetic reprogramming. Mice were randomized to receive a calorie restriction (CR), overweight (OW)-inducing, or diet-induced obesity (DIO) regimen (n = 27/group)...
April 3, 2017: Cancer Research
https://www.readbyqxmd.com/read/28368372/ercc1-xpf-cooperates-with-ctcf-and-cohesin-to%C3%A2-facilitate-the-developmental-silencing-of-imprinted%C3%A2-genes
#9
Georgia Chatzinikolaou, Zivkos Apostolou, Tamara Aid-Pavlidis, Anna Ioannidou, Ismene Karakasilioti, Giorgio L Papadopoulos, Michalis Aivaliotis, Maria Tsekrekou, John Strouboulis, Theodore Kosteas, George A Garinis
Inborn defects in DNA repair are associated with complex developmental disorders whose causal mechanisms are poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development...
April 3, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28336543/in-vivo-binding-of-prdm9-reveals-interactions-with-noncanonical-genomic-sites
#10
Corinne Grey, Julie A J Clément, Jérôme Buard, Benjamin Leblanc, Ivo Gut, Marta Gut, Laurent Duret, Bernard de Massy
In mouse and human meiosis, DNA double-strand breaks (DSBs) initiate homologous recombination and occur at specific sites called hotspots. The localization of these sites is determined by the sequence-specific DNA binding domain of the PRDM9 histone methyl transferase. Here, we performed an extensive analysis of PRDM9 binding in mouse spermatocytes. Unexpectedly, we identified a noncanonical recruitment of PRDM9 to sites that lack recombination activity and the PRDM9 binding consensus motif. These sites include gene promoters, where PRDM9 is recruited in a DSB-dependent manner...
April 2017: Genome Research
https://www.readbyqxmd.com/read/28334928/functional-assessment-of-ctcf-sites-at-cytokine-sensing-mammary-enhancers-using-crispr-cas9-gene-editing-in-mice
#11
Hye Kyung Lee, Michaela Willi, Chaochen Wang, Chul Min Yang, Harold E Smith, Chengyu Liu, Lothar Hennighausen
The zinc finger protein CTCF has been invoked in establishing boundaries between genes, thereby controlling spatial and temporal enhancer activities. However, there is limited genetic evidence to support the concept that these boundaries restrict the search space of enhancers. We have addressed this question in the casein locus containing five mammary and two non-mammary genes under the control of at least seven putative enhancers. We have identified two CTCF binding sites flanking the locus and two associated with a super-enhancer...
March 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28329684/cis-regulatory-circuits-regulating-nek6-kinase-overexpression-in-transformed-b-cells-are-super-enhancer-independent
#12
Yue Huang, Olivia I Koues, Jiang-Yang Zhao, Regina Liu, Sarah C Pyfrom, Jacqueline E Payton, Eugene M Oltz
Alterations in distal regulatory elements that control gene expression underlie many diseases, including cancer. Epigenomic analyses of normal and diseased cells have produced correlative predictions for connections between dysregulated enhancers and target genes involved in pathogenesis. However, with few exceptions, these predicted cis-regulatory circuits remain untested. Here, we dissect cis-regulatory circuits that lead to overexpression of NEK6, a mitosis-associated kinase, in human B cell lymphoma. We find that only a minor subset of predicted enhancers is required for NEK6 expression...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28319062/ctcf-genetic-alterations-in-endometrial-carcinoma-are-pro-tumorigenic
#13
A D Marshall, C G Bailey, K Champ, M Vellozzi, P O'Young, C Metierre, Y Feng, A Thoeng, A M Richards, U Schmitz, M Biro, R Jayasinghe, L Ding, L Anderson, E R Mardis, J E J Rasko
CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF haploinsufficiency through nonsense-mediated decay of mutant transcripts, or loss-of-function missense mutation. Conversely, we identified a recurrent CTCF mutation K365T, which alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28286735/mitotic-phosphorylation-of-ccctc-binding-factor-ctcf-reduces-its-dna-binding-activity
#14
Takeshi Sekiya, Kensaku Murano, Kohsuke Kato, Atsushi Kawaguchi, Kyosuke Nagata
During mitosis, higher order chromatin structures are disrupted and chromosomes are condensed to achieve accurate chromosome segregation. CCCTC-binding factor (CTCF) is a highly conserved and ubiquitously expressed C2H2-type zinc finger protein which is considered to be involved in epigenetic memory through regulation of higher order chromatin architecture. However, the regulatory mechanism of CTCF in mitosis is still unclear. Here we found that the DNA-binding activity of CTCF is regulated in a phosphorylation-dependent manner during mitosis...
March 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28282578/aberrant-methylation-patterns-affect-the-molecular-pathogenesis-of-rheumatoid-arthritis
#15
Yang Lin, Zhengqiang Luo
This study aims to investigate DNA methylation signatures in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA), and to explore the relationship with transcription factors (TFs) that help to distinguish RA from osteoarthritis (OA). Microarray dataset of GSE46346, including six FLS samples from patients with RA and five FLS samples from patients with OA, was downloaded from the Gene Expression Omnibus database. RA and OA samples were screened for differentially methylated loci (DMLs)...
March 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28282036/heterarchy-of-transcription-factors-driving-basal-and-luminal-cell-phenotypes-in-human-urothelium
#16
Carl Fishwick, Janet Higgins, Lawrence Percival-Alwyn, Arianna Hustler, Joanna Pearson, Sarah Bastkowski, Simon Moxon, David Swarbreck, Chris D Greenman, Jennifer Southgate
Cell differentiation is affected by complex networks of transcription factors that co-ordinate re-organisation of the chromatin landscape. The hierarchies of these relationships can be difficult to dissect. During in vitro differentiation of normal human uro-epithelial cells, formaldehyde-assisted isolation of regulatory elements (FAIRE-seq) and RNA-seq was used to identify alterations in chromatin accessibility and gene expression changes following activation of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) as a differentiation-initiating event...
March 10, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28262757/ctcf-participates-in-dna-damage-response-via-poly-adp-ribosyl-ation
#17
Deqiang Han, Qian Chen, Jiazhong Shi, Feng Zhang, Xiaochun Yu
CCCTC-binding factor (CTCF) plays an essential role in regulating the structure of chromatin by binding DNA strands for defining the boundary between active and heterochromatic DNA. However, the role of CTCF in DNA damage response remains elusive. Here, we show that CTCF is quickly recruited to the sites of DNA damage. The fast recruitment is mediated by the zinc finger domain and poly (ADP-ribose) (PAR). Further analyses show that only three zinc finger motifs are essential for PAR recognition. Moreover, CTCF-deficient cells are hypersensitive to genotoxic stress such as ionizing radiation (IR)...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28262505/distinct-roles-of-brd2-and-brd4-in-potentiating-the-transcriptional-program-for-th17-cell-differentiation
#18
Ka Lung Cheung, Fan Zhang, Anbalagan Jaganathan, Rajal Sharma, Qiang Zhang, Tsuyoshi Konuma, Tong Shen, June-Yong Lee, Chunyan Ren, Chih-Hung Chen, Geming Lu, Matthew R Olson, Weijia Zhang, Mark H Kaplan, Dan R Littman, Martin J Walsh, Huabao Xiong, Lei Zeng, Ming-Ming Zhou
The BET proteins are major transcriptional regulators and have emerged as new drug targets, but their functional distinction has remained elusive. In this study, we report that the BET family members Brd2 and Brd4 exert distinct genomic functions at genes whose transcription they co-regulate during mouse T helper 17 (Th17) cell differentiation. Brd2 is associated with the chromatin insulator CTCF and the cohesin complex to support cis-regulatory enhancer assembly for gene transcriptional activation. In this context, Brd2 binds the transcription factor Stat3 in an acetylation-sensitive manner and facilitates Stat3 recruitment to active enhancers occupied with transcription factors Irf4 and Batf...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28252665/chromatin-states-shape-insertion-profiles-of-the-piggybac-tol2-and-sleeping-beauty-transposons-and-murine-leukemia-virus
#19
Junko Yoshida, Keiko Akagi, Ryo Misawa, Chikara Kokubu, Junji Takeda, Kyoji Horie
DNA transposons and retroviruses are versatile tools in functional genomics and gene therapy. To facilitate their application, we conducted a genome-wide insertion site profiling of the piggyBac (PB), Tol2 and Sleeping Beauty (SB) transposons and the murine leukemia virus (MLV) in mouse embryonic stem cells (ESCs). PB and MLV preferred highly expressed genes, whereas Tol2 and SB preferred weakly expressed genes. However, correlations with DNase I hypersensitive sites were different for all vectors, indicating that chromatin accessibility is not the sole determinant...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28251841/topologically-associated-domains-a-successful-scaffold-for-the-evolution-of-gene-regulation-in-animals
#20
REVIEW
Rafael D Acemel, Ignacio Maeso, José Luis Gómez-Skarmeta
The evolution of gene regulation is considered one of the main drivers causing the astonishing morphological diversity in the animal kingdom. Gene regulation in animals heavily depends upon cis-regulatory elements, discrete pieces of DNA that interact with target promoters to regulate gene expression. In the last years, Chromosome Conformation Capture experiments (4C-seq, 5C, and HiC) in several organisms have shown that the genomes of many bilaterian animals are organized in the 3D chromatin space in compartments called topologically associated domains (TADs)...
March 2, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
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