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https://www.readbyqxmd.com/read/28334928/functional-assessment-of-ctcf-sites-at-cytokine-sensing-mammary-enhancers-using-crispr-cas9-gene-editing-in-mice
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28241063/role-of-dna-methylation-in-expression-control-of-the-ikzf3-gsdma-region-in-human-epithelial-cells
#11
Sanny Moussette, Abeer Al Tuwaijri, Hamid-Reza Kohan-Ghadr, Samar Elzein, Raquel Farias, Julie Bérubé, Bianca Ho, Catherine Laprise, Cynthia G Goodyer, Simon Rousseau, Anna K Naumova
Chromosomal region 17q12-q21 is associated with asthma and harbors regulatory polymorphisms that influence expression levels of all five protein-coding genes in the region: IKAROS family zinc finger 3 (Aiolos) (IKZF3), zona pellucida binding protein 2 (ZPBP2), ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), and gasdermins A and B (GSDMA, GSDMB). Furthermore, DNA methylation in this region has been implicated as a potential modifier of the genetic risk of asthma development. To further characterize the effect of DNA methylation, we examined the impact of treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) that causes DNA demethylation, on expression and promoter methylation of the five 17q12-q21 genes in the human airway epithelium cell line NuLi-1, embryonic kidney epithelium cell line 293T and human adenocarcinoma cell line MCF-7...
2017: PloS One
https://www.readbyqxmd.com/read/28196481/nuctools-analysis-of-chromatin-feature-occupancy-profiles-from-high-throughput-sequencing-data
#12
Yevhen Vainshtein, Karsten Rippe, Vladimir B Teif
BACKGROUND: Biomedical applications of high-throughput sequencing methods generate a vast amount of data in which numerous chromatin features are mapped along the genome. The results are frequently analysed by creating binary data sets that link the presence/absence of a given feature to specific genomic loci. However, the nucleosome occupancy or chromatin accessibility landscape is essentially continuous. It is currently a challenge in the field to cope with continuous distributions of deep sequencing chromatin readouts and to integrate the different types of discrete chromatin features to reveal linkages between them...
February 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28193136/ccctc-binding-factor-transcriptionally-targets-wdr5-to-mediate-somatic-cell-reprogramming
#13
Feng Wang, Jinghua Han, Li Wang, Ying Jing, Zhu Zhu, Dawei Hui, Zhaohui Wang, Yangzi Wang, Yang Dong, Tao Tan
It was previously reported that WD repeat domain 5 (Wdr5), a core member of the mammalian Trithorax complex, is a key regulator for the maintenance of embryonic stem (ES) cell pluripotency and somatic cell reprogramming. However, it remains unclear whether other factors are also involved in this process. Here, we show that CTCF is an upstream regulator of Wdr5: It physically associates with Wdr5 and further transcriptionally controls its expression by directly targeting the Wdr5 gene promoter. As a downstream effector, overexpression of Wdr5 can rescue ES cells from growth defects and decreased formation of induced pluripotent stem cells caused by CTCF knockdown...
March 20, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28178516/chromatin-states-in-mouse-sperm-correlate-with-embryonic-and-adult-regulatory-landscapes
#14
Yoon Hee Jung, Michael E G Sauria, Xiaowen Lyu, Manjinder S Cheema, Juan Ausio, James Taylor, Victor G Corces
The mammalian sperm genome is thought to lack substantial information for the regulation of future expression after fertilization. Here, we show that most promoters in mouse sperm are flanked by well-positioned nucleosomes marked by active histone modifications. Analysis of these modifications suggests that many enhancers and super-enhancers functional in embryonic and adult tissues are already specified in sperm. The sperm genome is bound by CTCF and cohesin at sites that are also present in round spermatids and embryonic stem cells (ESCs)...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28161276/erythroid-specific-activator-gata-1-dependent-interactions-between-ctcf-sites-around-the-%C3%AE-globin-locus
#15
Yujin Kang, Yea Woon Kim, Jin Kang, Won Ju Yun, AeRi Kim
CTCF sites (binding motifs for CCCTC-binding factor, an insulator protein) are located considerable distances apart on genomes but are closely positioned in organized chromatin. The close positioning of CTCF sites is often cell type or tissue specific. Here we analyzed chromatin organization in eight CTCF sites around the β-globin locus by 3C assay and explored the roles of erythroid specific transcription activator GATA-1 and KLF1 in it. It was found five CTCF sites convergent to the locus interact with each other in erythroid K562 cells but not in non-erythroid 293 cells...
February 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28150704/genome-wide-dna-methylation-reprogramming-in-response-to-inorganic-arsenic-links-inhibition-of-ctcf-binding-dnmt-expression-and-cellular-transformation
#16
Matthew Rea, Meredith Eckstein, Rebekah Eleazer, Caroline Smith, Yvonne N Fondufe-Mittendorf
Chronic low dose inorganic arsenic (iAs) exposure leads to changes in gene expression and epithelial-to-mesenchymal transformation. During this transformation, cells adopt a fibroblast-like phenotype accompanied by profound gene expression changes. While many mechanisms have been implicated in this transformation, studies that focus on the role of epigenetic alterations in this process are just emerging. DNA methylation controls gene expression in physiologic and pathologic states. Several studies show alterations in DNA methylation patterns in iAs-mediated pathogenesis, but these studies focused on single genes...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28145452/testis-specific-transcriptional-regulators-selectively-occupy-boris-bound-ctcf-target-regions-in-mouse-male-germ-cells
#17
Samuel Rivero-Hinojosa, Sungyun Kang, Victor V Lobanenkov, Gabriel E Zentner
Despite sharing the same sequence specificity in vitro and in vivo, CCCTC-binding factor (CTCF) and its paralog brother of the regulator of imprinted sites (BORIS) are simultaneously expressed in germ cells. Recently, ChIP-seq analysis revealed two classes of CTCF/BORIS-bound regions: single CTCF target sites (1xCTSes) that are bound by CTCF alone (CTCF-only) or double CTCF target sites (2xCTSes) simultaneously bound by CTCF and BORIS (CTCF&BORIS) or BORIS alone (BORIS-only) in germ cells and in BORIS-positive somatic cancer cells...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28139744/transcriptional-heterogeneity-in-the-lactase-gene-within-cell-type-is-linked-to-the-epigenome
#18
Edward Oh, Richie Jeremian, Gabriel Oh, Daniel Groot, Miki Susic, KwangHo Lee, Kelly Foy, Peter W Laird, Arturas Petronis, Viviane Labrie
Transcriptional variation in histologically- and genetically- identical cells is a widespread phenomenon in tissues, yet the processes conferring this heterogeneity are not well understood. To identify contributing factors, we analyzed epigenetic profiles associated with the in vivo transcriptional gradient of the mouse lactase gene (Lct), which occurs in enterocytes along the proximal-to-distal axis of the small intestine. We found that epigenetic signatures at enhancer and promoter elements aligns with transcriptional variation of Lct in enterocytes...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28137913/chromatin-domain-organization-of-tcrb-locus-and-its-perturbation-by-ectopic-ctcf-binding
#19
Pratishtha Rawat, Manisha Jalan, Ananya Sadhu, Abhilasha Kanaujia, Madhulika Srivastava
CTCF mediated chromatin interactions influence organization and function of mammalian genome in diverse ways. We analyzed the interactions amongst CTCF binding sites (CBS) at murine TCRb locus to discern the role of CTCF mediated interactions in regulation of transcription and VDJ recombination. 3C analysis revealed thymocyte specific long-range intrachromosomal interactions amongst various CBS across the locus that were relevant for defining the limit of enhancer Eb regulated Recombination Centre (RC) and for facilitating the spatial proximity of Trbv segments to RC...
January 30, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28137821/improved-genome-assembly-of-american-alligator-genome-reveals-conserved-architecture-of-estrogen-signaling
#20
Edward Stallknecht Rice, Satomi Kohno, John St John, Son Pham, Jonathan Howard, Liana Lareau, Brendan L O'Connell, Glenn Hickey, Joel Armstrong, Alden Deran, Ian Fiddes, Roy N Platt, Cathy Gresham, Fiona McCarthy, Colin Kern, David Haan, Tan Phan, Carl Schmidt, Jeremy R Sanford, David A Ray, Benedict Paten, Louis J Guillette, Richard E Green
The American alligator, Alligator mississippiensis, like all crocodilians, has temperature-dependent sex determination, in which the sex of an embryo is determined by the incubation temperature of the egg during a critical period of development. The lack of genetic differences between male and female alligators leaves open the question of how the genes responsible for sex determination and differentiation are regulated. One insight into this question comes from the fact that exposing an embryo incubated at male-producing temperature to estrogen causes it to develop ovaries...
January 30, 2017: Genome Research
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