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https://www.readbyqxmd.com/read/29344104/x-inactive-specific-transcript-of-peripheral-blood-cells-is-regulated-by-exosomal-jpx-and-acts-as-a-biomarker-for-female-patients-with-hepatocellular-carcinoma
#1
Xiang Ma, Tingdong Yuan, Chao Yang, Zusen Wang, Yunjin Zang, Liqun Wu, Likun Zhuang
Background: Long noncoding ribonucleic acid (lncRNA) X-inactive-specific transcript (Xist) was reported to affect cell proliferation and metastasis in hepatocellular carcinoma (HCC). However, there are rare reports focusing on the diagnostic evaluation and regulatory mechanism of Xist expression from peripheral blood cells of patients with HCC. Methods: In this study, a cohort of 206 female participants including healthy volunteers (HVs) and patients with chronic hepatitis B (CHB), cirrhosis and HCC was recruited...
November 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29341686/nonequilibrium-chromosome-looping-via-molecular-slip-links
#2
C A Brackley, J Johnson, D Michieletto, A N Morozov, M Nicodemi, P R Cook, D Marenduzzo
We propose a model for the formation of chromatin loops based on the diffusive sliding of molecular slip links. These mimic the behavior of molecules like cohesin, which, along with the CTCF protein, stabilize loops which contribute to organizing the genome. By combining 3D Brownian dynamics simulations and 1D exactly solvable nonequilibrium models, we show that diffusive sliding is sufficient to account for the strong bias in favor of convergent CTCF-mediated chromosome loops observed experimentally. We also find that the diffusive motion of multiple slip links along chromatin is rectified by an intriguing ratchet effect that arises if slip links bind to the chromatin at a preferred "loading site...
September 29, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/29339716/to-explore-the-mechanism-of-the-grm4-gene-in-osteosarcoma-by-rna-sequencing-and-bioinformatics-approach
#3
Yunguo Pang, Jinmin Zhao, Mitra Fowdur, Yun Liu, Hao Wu, Maolin He
BACKGROUND Glutamate metabotropic receptor 4 (GRM4) has been correlated with the pathogenesis of osteosarcoma. The objective of this study was to explore the underlying molecular mechanism of GRM4 in osteosarcoma. MATERIAL AND METHODS The expression levels of GRM4 in four human osteosarcoma cell lines and hFOB1.19 cells were examined by real-time quantitative PCR (RT-qPCR). The U2OS cells of the highest GRM4 expression were transfected with lentivirus-mediated small interfering RNA (siRNA). The differentially expressed genes (DEGs) after GRM4 gene silencing were screened through RNA sequencing, and analyzed by bioinformatics...
January 17, 2018: Medical Science Monitor Basic Research
https://www.readbyqxmd.com/read/29335486/high-resolution-tads-reveal-dna-sequences-underlying-genome-organization-in-flies
#4
Fidel Ramírez, Vivek Bhardwaj, Laura Arrigoni, Kin Chung Lam, Björn A Grüning, José Villaveces, Bianca Habermann, Asifa Akhtar, Thomas Manke
Despite an abundance of new studies about topologically associating domains (TADs), the role of genetic information in TAD formation is still not fully understood. Here we use our software, HiCExplorer (hicexplorer.readthedocs.io) to annotate >2800 high-resolution (570 bp) TAD boundaries in Drosophila melanogaster. We identify eight DNA motifs enriched at boundaries, including a motif bound by the M1BP protein, and two new boundary motifs. In contrast to mammals, the CTCF motif is only enriched on a small fraction of boundaries flanking inactive chromatin while most active boundaries contain the motifs bound by the M1BP or Beaf-32 proteins...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29335463/sub-kb-hi-c-in-d-melanogaster-reveals-conserved-characteristics-of-tads-between-insect-and-mammalian-cells
#5
Qi Wang, Qiu Sun, Daniel M Czajkowsky, Zhifeng Shao
Topologically associating domains (TADs) are fundamental elements of the eukaryotic genomic structure. However, recent studies suggest that the insulating complexes, CTCF/cohesin, present at TAD borders in mammals are absent from those in Drosophila melanogaster, raising the possibility that border elements are not conserved among metazoans. Using in situ Hi-C with sub-kb resolution, here we show that the D. melanogaster genome is almost completely partitioned into >4000 TADs, nearly sevenfold more than previously identified...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316705/translocation-breakpoints-preferentially-occur-in-euchromatin-and-acrocentric-chromosomes
#6
Cheng-Yu Lin, Ankit Shukla, John P Grady, J Lynn Fink, Eloise Dray, Pascal H G Duijf
Chromosomal translocations drive the development of many hematological and some solid cancers. Several factors have been identified to explain the non-random occurrence of translocation breakpoints in the genome. These include chromatin density, gene density and CCCTC-binding factor (CTCF)/cohesin binding site density. However, such factors are at least partially interdependent. Using 13,844 and 1563 karyotypes from human blood and solid cancers, respectively, our multiple regression analysis only identified chromatin density as the primary statistically significant predictor...
January 8, 2018: Cancers
https://www.readbyqxmd.com/read/29312684/respecting-boundaries-ctcf-chromatin-structural-organization-and-heart-failure
#7
EDITORIAL
Ashley J Sizer, Kathleen A Martin
No abstract text is available yet for this article.
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29307778/computational-and-functional-characterization-of-four-snps-in-the-sost-locus-associated-with-osteoporosis
#8
Weiyuan Ye, Ya Wang, Bing Mei, Sasa Hou, Xinhong Liu, Guiju Wu, Longjuan Qin, Kehui Zhao, Qingyang Huang
The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. Numerous single nucleotide polymorphisms (SNPs) in the SOST locus are firmly associated with bone mineral density (BMD) and fracture in genome-wide association studies (GWAS) and candidate gene association studies. However, the validation and mechanistic elucidation of causal genetic variants, especially for SNPs located beyond the promoter-proximal region, remain largely unresolved...
January 4, 2018: Bone
https://www.readbyqxmd.com/read/29307136/ctcf-cohesin-and-chromatin-in-human-cancer
#9
REVIEW
Sang-Hyun Song, Tae-You Kim
It is becoming increasingly clear that eukaryotic genomes are subjected to higher-order chromatin organization by the CCCTC-binding factor/cohesin complex. Their dynamic interactions in three dimensions within the nucleus regulate gene transcription by changing the chromatin architecture. Such spatial genomic organization is functionally important for the spatial disposition of chromosomes to control cell fate during development and differentiation. Thus, the dysregulation of proper long-range chromatin interactions may influence the development of tumorigenesis and cancer progression...
December 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/29300120/extrusion-without-a-motor-a-new-take-on-the-loop-extrusion-model-of-genome-organization
#10
C A Brackley, J Johnson, D Michieletto, A N Morozov, M Nicodemi, P R Cook, D Marenduzzo
Chromatin loop extrusion is a popular model for the formation of CTCF loops and topological domains. Recent HiC data have revealed a strong bias in favour of a particular arrangement of the CTCF binding motifs that stabilize loops, and extrusion is the only model to date which can explain this. However, the model requires a motor to generate the loops, and although cohesin is a strong candidate for the extruding factor, a suitable motor protein (or a motor activity in cohesin itself) has yet to be found. Here we explore a new hypothesis: that there is no motor, and thermal motion within the nucleus drives extrusion...
January 4, 2018: Nucleus
https://www.readbyqxmd.com/read/29273679/the-hoxd-cluster-is-a-dynamic-and-resilient-tad-boundary-controlling-the-segregation-of-antagonistic-regulatory-landscapes
#11
Eddie Rodríguez-Carballo, Lucille Lopez-Delisle, Ye Zhan, Pierre J Fabre, Leonardo Beccari, Imane El-Idrissi, Thi Hanh Nguyen Huynh, Hakan Ozadam, Job Dekker, Denis Duboule
The mammalian HoxD cluster lies between two topologically associating domains (TADs) matching distinct enhancer-rich regulatory landscapes. During limb development, the telomeric TAD controls the early transcription of Hoxd genes in forearm cells, whereas the centromeric TAD subsequently regulates more posterior Hoxd genes in digit cells. Therefore, the TAD boundary prevents the terminal Hoxd13 gene from responding to forearm enhancers, thereby allowing proper limb patterning. To assess the nature and function of this CTCF-rich DNA region in embryos, we compared chromatin interaction profiles between proximal and distal limb bud cells isolated from mutant stocks where various parts of this boundary region were removed...
December 22, 2017: Genes & Development
https://www.readbyqxmd.com/read/29273625/the-nuclear-matrix-protein-hnrnpu-maintains-3d-genome-architecture-globally-in-mouse-hepatocytes
#12
Hui Fan, Pin Lv, Xiangru Huo, Jicheng Wu, Qianfeng Wang, Lu Cheng, Yun Liu, Qiqun Tang, Ling Zhang, Feng Zhang, Xiaoqi Zheng, Hao Wu, Bo Wen
The eukaryotic chromosomes are folded into higher-order conformation to coordinate genome functions. Besides long-range chromatin loops, recent chromosome conformation capture (3C)-based studies indicated the higher level of chromatin structures including compartments and topologically associating domains (TADs), which may serve as units of genome organization and functions. However, the molecular machinery underlying these hierarchically three-dimensional (3D) chromatin architectures remains poorly understood...
December 22, 2017: Genome Research
https://www.readbyqxmd.com/read/29235471/ctcf-driven-terra-transcription-facilitates-completion-of-telomere-dna-replication
#13
Kate Beishline, Olga Vladimirova, Stephen Tutton, Zhuo Wang, Zhong Deng, Paul M Lieberman
Telomere repeat DNA forms a nucleo-protein structure that can obstruct chromosomal DNA replication, especially under conditions of replication stress. Transcription of telomere repeats can initiate at subtelomeric CTCF-binding sites to generate telomere repeat-encoding RNA (TERRA), but the role of transcription, CTCF, and TERRA in telomere replication is not known. Here, we have used CRISPR/Cas9 gene editing to mutate CTCF-binding sites at the putative start site of TERRA transcripts for a class of subtelomeres...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29234056/identification-and-characterization-of-two-functional-variants-in-the-human-longevity-gene-foxo3
#14
Friederike Flachsbart, Janina Dose, Liljana Gentschew, Claudia Geismann, Amke Caliebe, Carolin Knecht, Marianne Nygaard, Nandini Badarinarayan, Abdou ElSharawy, Sandra May, Anne Luzius, Guillermo G Torres, Marlene Jentzsch, Michael Forster, Robert Häesler, Kathrin Pallauf, Wolfgang Lieb, Céline Derbois, Pilar Galan, Dmitriy Drichel, Alexander Arlt, Andreas Till, Ben Krause-Kyora, Gerald Rimbach, Hélène Blanché, Jean-François Deleuze, Lene Christiansen, Kaare Christensen, Michael Nothnagel, Philip Rosenstiel, Stefan Schreiber, Andre Franke, Susanne Sebens, Almut Nebel
FOXO3 is consistently annotated as a human longevity gene. However, functional variants and underlying mechanisms for the association remain unknown. Here, we perform resequencing of the FOXO3 locus and single-nucleotide variant (SNV) genotyping in three European populations. We find two FOXO3 SNVs, rs12206094 and rs4946935, to be most significantly associated with longevity and further characterize them functionally. We experimentally validate the in silico predicted allele-dependent binding of transcription factors (CTCF, SRF) to the SNVs...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29228930/gene-expression-analysis-in-asthma-using-a-targeted-multiplex-array
#15
Christopher D Pascoe, Ma'en Obeidat, Bryna A Arsenault, Yunlong Nie, Stephanie Warner, Dorota Stefanowicz, Samuel J Wadsworth, Jeremy A Hirota, S Jasemine Yang, Delbert R Dorscheid, Chris Carlsten, Tillie L Hackett, Chun Y Seow, Peter D Paré
BACKGROUND: Gene expression changes in the structural cells of the airways are thought to play a role in the development of asthma and airway hyperresponsiveness. This includes changes to smooth muscle contractile machinery and epithelial barrier integrity genes. We used a targeted gene expression arrays to identify changes in the expression and co-expression of genes important in asthma pathology. METHODS: RNA was isolated from the airways of donor lungs from 12 patients with asthma (8 fatal) and 12 non-asthmatics controls and analyzed using a multiplexed, hypothesis-directed platform to detect differences in gene expression...
December 11, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29225036/transcription-and-remodeling-produce-asymmetrically-unwrapped-nucleosomal-intermediates
#16
Srinivas Ramachandran, Kami Ahmad, Steven Henikoff
Nucleosomes are disrupted during transcription and other active processes, but the structural intermediates during nucleosome disruption in vivo are unknown. To identify intermediates, we mapped subnucleosomal protections in Drosophila cells using Micrococcal Nuclease followed by sequencing. At the first nucleosome position downstream of the transcription start site, we identified unwrapped intermediates, including hexasomes that lack either proximal or distal contacts. Inhibiting topoisomerases or depleting histone chaperones increased unwrapping, whereas inhibiting release of paused RNAPII or reducing RNAPII elongation decreased unwrapping...
December 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29224777/yy1-is-a-structural-regulator-of-enhancer-promoter-loops
#17
Abraham S Weintraub, Charles H Li, Alicia V Zamudio, Alla A Sigova, Nancy M Hannett, Daniel S Day, Brian J Abraham, Malkiel A Cohen, Behnam Nabet, Dennis L Buckley, Yang Eric Guo, Denes Hnisz, Rudolf Jaenisch, James E Bradner, Nathanael S Gray, Richard A Young
There is considerable evidence that chromosome structure plays important roles in gene control, but we have limited understanding of the proteins that contribute to structural interactions between gene promoters and their enhancer elements. Large DNA loops that encompass genes and their regulatory elements depend on CTCF-CTCF interactions, but most enhancer-promoter interactions do not employ this structural protein. Here, we show that the ubiquitously expressed transcription factor Yin Yang 1 (YY1) contributes to enhancer-promoter structural interactions in a manner analogous to DNA interactions mediated by CTCF...
November 30, 2017: Cell
https://www.readbyqxmd.com/read/29217591/topologically-associating-domains-and-chromatin-loops-depend-on-cohesin-and-are-regulated-by-ctcf-wapl-and-pds5-proteins
#18
Gordana Wutz, Csilla Várnai, Kota Nagasaka, David A Cisneros, Roman R Stocsits, Wen Tang, Stefan Schoenfelder, Gregor Jessberger, Matthias Muhar, M Julius Hossain, Nike Walther, Birgit Koch, Moritz Kueblbeck, Jan Ellenberg, Johannes Zuber, Peter Fraser, Jan-Michael Peters
Mammalian genomes are spatially organized into compartments, topologically associating domains (TADs), and loops to facilitate gene regulation and other chromosomal functions. How compartments, TADs, and loops are generated is unknown. It has been proposed that cohesin forms TADs and loops by extruding chromatin loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here, we show that cohesin suppresses compartments but is required for TADs and loops, that CTCF defines their boundaries, and that the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops...
December 7, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29212169/ccctc-binding-factor-inhibits-breast-cancer-cell-proliferation-and-metastasis-via-inactivation-of-the-nuclear-factor-kappab-pathway
#19
Jie Wu, Peng-Chang Li, Jun-Yi Pang, Guo-You Liu, Xue-Min Xie, Jia-Yao Li, Yi-Cong Yin, Jian-Hua Han, Xiu-Zhi Guo, Ling Qiu
CCCTC-binding factor (CTCF) is an important epigenetic regulator implicated in multiple cellular processes, including growth, proliferation, differentiation, and apoptosis. Although CTCF deletion or mutation has been associated with human breast cancer, the role of CTCF in breast cancer is questionable. We investigated the biological functions of CTCF in breast cancer and the underlying mechanism. The results showed that CTCF expression in human breast cancer cells and tissues was significantly lower than that in normal breast cells and tissues...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29199022/ctcf-mediated-chromatin-loops-between-promoter-and-gene-body-regulate-alternative-splicing-across-individuals
#20
Mariana Ruiz-Velasco, Manjeet Kumar, Mang Ching Lai, Pooja Bhat, Ana Belen Solis-Pinson, Alejandro Reyes, Stefan Kleinsorg, Kyung-Min Noh, Toby J Gibson, Judith B Zaugg
The CCCTC-binding factor (CTCF) is known to establish long-range DNA contacts that alter the three-dimensional architecture of chromatin, but how the presence of CTCF influences nearby gene expression is still poorly understood. Here, we analyze CTCF chromatin immunoprecipitation sequencing, RNA sequencing, and Hi-C data, together with genotypes from a healthy human cohort, and measure statistical associations between inter-individual variability in CTCF binding and alternative exon usage. We demonstrate that CTCF-mediated chromatin loops between promoters and intragenic regions are prevalent and that when exons are in physical proximity with their promoters, CTCF binding correlates with exon inclusion in spliced mRNA...
November 24, 2017: Cell Systems
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