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Ctcf cohesin

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https://www.readbyqxmd.com/read/28178516/chromatin-states-in-mouse-sperm-correlate-with-embryonic-and-adult-regulatory-landscapes
#1
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/28107481/bet-inhibitors-disrupt-rad21-dependent-conformational-control-of-kshv-latency
#2
Horng-Shen Chen, Alessandra De Leo, Zhuo Wang, Andrew Kerekovic, Robert Hills, Paul M Lieberman
Kaposi's Sarcoma-associated Herpesvirus (KSHV) establishes stable latent infection in B-lymphocytes and pleural effusion lymphomas (PELs). During latency, the viral genome persists as an epigenetically constrained episome with restricted gene expression programs. To identify epigenetic regulators of KSHV latency, we screened a focused small molecule library containing known inhibitors of epigenetic factors. We identified JQ1, a Bromodomain and Extended Terminal (BET) protein inhibitor, as a potent activator of KSHV lytic reactivation from B-cells carrying episomal KSHV...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/27974201/functional-mutations-form-at-ctcf-cohesin-binding-sites-in-melanoma-due-to-uneven-nucleotide-excision-repair-across-the-motif
#3
Rebecca C Poulos, Julie A I Thoms, Yi Fang Guan, Ashwin Unnikrishnan, John E Pimanda, Jason W H Wong
CTCF binding sites are frequently mutated in cancer, but how these mutations accumulate and whether they broadly perturb CTCF binding are not well understood. Here, we report that skin cancers exhibit a highly specific asymmetric mutation pattern within CTCF motifs attributable to ultraviolet irradiation and differential nucleotide excision repair (NER). CTCF binding site mutations form independently of replication timing and are enriched at sites of CTCF/cohesin complex binding, suggesting a role for cohesin in stabilizing CTCF-DNA binding and impairing NER...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880868/origin-and-evolution-of-the-metazoan-non-coding-regulatory-genome
#4
REVIEW
Federico Gaiti, Andrew D Calcino, Miloš Tanurdžić, Bernard M Degnan
Animals rely on genomic regulatory systems to direct the dynamic spatiotemporal and cell-type specific gene expression that is essential for the development and maintenance of a multicellular lifestyle. Although it is widely appreciated that these systems ultimately evolved from genomic regulatory mechanisms present in single-celled stem metazoans, it remains unclear how this occurred. Here, we focus on the contribution of the non-coding portion of the genome to the evolution of animal gene regulation, specifically on recent insights from non-bilaterian metazoan lineages, and unicellular and colonial holozoan sister taxa...
November 20, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27863240/insulated-neighborhoods-structural-and-functional-units-of-mammalian-gene-control
#5
REVIEW
Denes Hnisz, Daniel S Day, Richard A Young
Understanding how transcriptional enhancers control over 20,000 protein-coding genes to maintain cell-type-specific gene expression programs in all human cells is a fundamental challenge in regulatory biology. Recent studies suggest that gene regulatory elements and their target genes generally occur within insulated neighborhoods, which are chromosomal loop structures formed by the interaction of two DNA sites bound by the CTCF protein and occupied by the cohesin complex. Here, we review evidence that insulated neighborhoods provide for specific enhancer-gene interactions, are essential for both normal gene activation and repression, form a chromosome scaffold that is largely preserved throughout development, and are perturbed by genetic and epigenetic factors in disease...
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27851967/a-compendium-of-chromatin-contact-maps-reveals-spatially-active-regions-in-the-human-genome
#6
Anthony D Schmitt, Ming Hu, Inkyung Jung, Zheng Xu, Yunjiang Qiu, Catherine L Tan, Yun Li, Shin Lin, Yiing Lin, Cathy L Barr, Bing Ren
The three-dimensional configuration of DNA is integral to all nuclear processes in eukaryotes, yet our knowledge of the chromosome architecture is still limited. Genome-wide chromosome conformation capture studies have uncovered features of chromatin organization in cultured cells, but genome architecture in human tissues has yet to be explored. Here, we report the most comprehensive survey to date of chromatin organization in human tissues. Through integrative analysis of chromatin contact maps in 21 primary human tissues and cell types, we find topologically associating domains highly conserved in different tissues...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27799150/rapid-movement-and-transcriptional-re-localization-of-human-cohesin-on-dna
#7
Iain F Davidson, Daniela Goetz, Maciej P Zaczek, Maxim I Molodtsov, Pim J Huis In 't Veld, Florian Weissmann, Gabriele Litos, David A Cisneros, Maria Ocampo-Hafalla, Rene Ladurner, Frank Uhlmann, Alipasha Vaziri, Jan-Michael Peters
The spatial organization, correct expression, repair, and segregation of eukaryotic genomes depend on cohesin, ring-shaped protein complexes that are thought to function by entrapping DNA It has been proposed that cohesin is recruited to specific genomic locations from distal loading sites by an unknown mechanism, which depends on transcription, and it has been speculated that cohesin movements along DNA could create three-dimensional genomic organization by loop extrusion. However, whether cohesin can translocate along DNA is unknown...
December 15, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27742736/cohesin-mutations-in-cancer
#8
Magali De Koninck, Ana Losada
Cohesin is a large ring-shaped protein complex, conserved from yeast to human, which participates in most DNA transactions that take place in the nucleus. It mediates sister chromatid cohesion, which is essential for chromosome segregation and homologous recombination (HR)-mediated DNA repair. Together with architectural proteins and transcriptional regulators, such as CTCF and Mediator, respectively, it contributes to genome organization at different scales and thereby affects transcription, DNA replication, and locus rearrangement...
December 1, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27669308/making-sense-of-the-tangle-insights-into-chromatin-folding-and-gene-regulation
#9
REVIEW
Ill-Min Chung, Sarada Ketharnathan, Seung-Hyun Kim, Muthu Thiruvengadam, Mari Kavitha Rani, Govindasamy Rajakumar
Proximity ligation assays such as circularized chromosome conformation capture and high-throughput chromosome capture assays have shed light on the structural organization of the interphase genome. Functional topologically associating domains (TADs) that constitute the building blocks of genomic organization are disrupted and reconstructed during the cell cycle. Epigenetic memory, as well as the sequence of chromosomes, regulate TAD reconstitution. Sub-TAD domains that are invariant across cell types have been identified, and contacts between these domains, rather than looping, are speculated to drive chromatin folding...
2016: Genes
https://www.readbyqxmd.com/read/27625394/maps-of-context-dependent-putative-regulatory-regions-and-genomic-signal-interactions
#10
Klev Diamanti, Husen M Umer, Marcin Kruczyk, Michał J Dąbrowski, Marco Cavalli, Claes Wadelius, Jan Komorowski
Gene transcription is regulated mainly by transcription factors (TFs). ENCODE and Roadmap Epigenomics provide global binding profiles of TFs, which can be used to identify regulatory regions. To this end we implemented a method to systematically construct cell-type and species-specific maps of regulatory regions and TF-TF interactions. We illustrated the approach by developing maps for five human cell-lines and two other species. We detected ∼144k putative regulatory regions among the human cell-lines, with the majority of them being ∼300 bp...
September 12, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27607579/distal-regulation-of-c-myb-expression-during-il-6-induced-differentiation-in-murine-myeloid-progenitor-m1-cells
#11
Junfang Zhang, Bingshe Han, Xiaoxia Li, Juraj Bies, Penglei Jiang, Richard P Koller, Linda Wolff
The c-Myb transcription factor is a major regulator that controls differentiation and proliferation of hematopoietic progenitor cells, which is frequently deregulated in hematological diseases, such as lymphoma and leukemia. Understanding of the mechanisms regulating the transcription of c-myb gene is challenging as it lacks a typical promoter and multiple factors are involved. Our previous studies identified some distal regulatory elements in the upstream regions of c-myb gene in murine myeloid progenitor M1 cells, but the detailed mechanisms still remain unclear...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27582050/topoisomerase-ii-beta-interacts-with-cohesin-and-ctcf-at-topological-domain-borders
#12
Liis Uusküla-Reimand, Huayun Hou, Payman Samavarchi-Tehrani, Matteo Vietri Rudan, Minggao Liang, Alejandra Medina-Rivera, Hisham Mohammed, Dominic Schmidt, Petra Schwalie, Edwin J Young, Jüri Reimand, Suzana Hadjur, Anne-Claude Gingras, Michael D Wilson
BACKGROUND: Type II DNA topoisomerases (TOP2) regulate DNA topology by generating transient double stranded breaks during replication and transcription. Topoisomerase II beta (TOP2B) facilitates rapid gene expression and functions at the later stages of development and differentiation. To gain new insight into the genome biology of TOP2B, we used proteomics (BioID), chromatin immunoprecipitation, and high-throughput chromosome conformation capture (Hi-C) to identify novel proximal TOP2B protein interactions and characterize the genomic landscape of TOP2B binding at base pair resolution...
2016: Genome Biology
https://www.readbyqxmd.com/read/27543316/mutations-of-myelodysplastic-syndromes-mds-an-update
#13
REVIEW
Bani Bandana Ganguly, N N Kadam
The plethora of knowledge gained on myelodysplastic syndromes (MDS), a heterogeneous pre-malignant disorder of hematopoietic stem cells, through sequencing of several pathway genes has unveiled molecular pathogenesis and its progression to AML. Evolution of phenotypic classification and risk-stratification based on peripheral cytopenias and blast count has moved to five-tier risk-groups solely concerning chromosomal aberrations. Increased frequency of complex abnormalities, which is associated with genetic instability, defines the subgroup of worst prognosis in MDS...
July 2016: Mutation Research. Reviews in Mutation Research
https://www.readbyqxmd.com/read/27526722/motif-oriented-high-resolution-analysis-of-chip-seq-data-reveals-the-topological-order-of-ctcf-and-cohesin-proteins-on-dna
#14
Gergely Nagy, Erik Czipa, László Steiner, Tibor Nagy, Sándor Pongor, László Nagy, Endre Barta
BACKGROUND: ChIP-seq provides a wealth of information on the approximate location of DNA-binding proteins genome-wide. It is known that the targeted motifs in most cases can be found at the peak centers. A high resolution mapping of ChIP-seq peaks could in principle allow the fine mapping of the protein constituents within protein complexes, but the current ChIP-seq analysis pipelines do not target the basepair resolution strand specific mapping of peak summits. RESULTS: The approach proposed here is based on i) locating regions that are bound by a sufficient number of proteins constituting a complex; ii) determining the position of the underlying motif using either a direct or a de novo motif search approach; and iii) determining the exact location of the peak summits with respect to the binding motif in a strand specific manner...
2016: BMC Genomics
https://www.readbyqxmd.com/read/27414788/-znf143-is-involved-in-ctcf-mediated-chromatin-interactions-by-cooperation-with-cohesin-and-other-partners
#15
B-Y Ye, W-L Shen, D Wang, P Li, Z Zhang, M-L Shi, Y Zhang, F-X Zhang, Z-H Zhao
ZNF143 is a ubiquitously expressed transcription factor conserved in vertebrates and might regulate the expression of numerous genes. But its function in mediating chromatin interactions remains elusive. By integrated analysis of public datasets, we provided evidence that a majority of ZNF143 binding sites (BSs) were involved in CTCF-mediated chromatin interaction networks (CTCF-CINs) by overlapping with cohesin-BSs and CTCF-BSs. We further showed that only a very few CTCF-CINs were associated with ZNF143 alone, whereas those associated with ZNF143 and cohesin simultaneously were highly overlapped with constitutive, conserved CTCF-BSs and enriched at boundaries of chromatin topologically associating domains...
May 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27219007/ctcf-and-cohesinsa-1-mark-active-promoters-and-boundaries-of-repressive-chromatin-domains-in-primary-human-erythroid-cells
#16
Laurie A Steiner, Vincent Schulz, Yelena Makismova, Kimberly Lezon-Geyda, Patrick G Gallagher
BACKGROUND: CTCF and cohesinSA-1 are regulatory proteins involved in a number of critical cellular processes including transcription, maintenance of chromatin domain architecture, and insulator function. To assess changes in the CTCF and cohesinSA-1 interactomes during erythropoiesis, chromatin immunoprecipitation coupled with high throughput sequencing and mRNA transcriptome analyses via RNA-seq were performed in primary human hematopoietic stem and progenitor cells (HSPC) and primary human erythroid cells from single donors...
2016: PloS One
https://www.readbyqxmd.com/read/27210764/formation-of-chromosomal-domains-by-loop-extrusion
#17
Geoffrey Fudenberg, Maxim Imakaev, Carolyn Lu, Anton Goloborodko, Nezar Abdennur, Leonid A Mirny
Topologically associating domains (TADs) are fundamental structural and functional building blocks of human interphase chromosomes, yet the mechanisms of TAD formation remain unclear. Here, we propose that loop extrusion underlies TAD formation. In this process, cis-acting loop-extruding factors, likely cohesins, form progressively larger loops but stall at TAD boundaries due to interactions with boundary proteins, including CTCF. Using polymer simulations, we show that this model produces TADs and finer-scale features of Hi-C data...
May 31, 2016: Cell Reports
https://www.readbyqxmd.com/read/27203237/computational-identification-of-genomic-features-that-influence-3d-chromatin-domain-formation
#18
Raphaël Mourad, Olivier Cuvier
Recent advances in long-range Hi-C contact mapping have revealed the importance of the 3D structure of chromosomes in gene expression. A current challenge is to identify the key molecular drivers of this 3D structure. Several genomic features, such as architectural proteins and functional elements, were shown to be enriched at topological domain borders using classical enrichment tests. Here we propose multiple logistic regression to identify those genomic features that positively or negatively influence domain border establishment or maintenance...
May 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27135601/long-range-chromosome-interactions-mediated-by-cohesin-shape-circadian-gene-expression
#19
Yichi Xu, Weimin Guo, Ping Li, Yan Zhang, Meng Zhao, Zenghua Fan, Zhihu Zhao, Jun Yan
Mammalian circadian rhythm is established by the negative feedback loops consisting of a set of clock genes, which lead to the circadian expression of thousands of downstream genes in vivo. As genome-wide transcription is organized under the high-order chromosome structure, it is largely uncharted how circadian gene expression is influenced by chromosome architecture. We focus on the function of chromatin structure proteins cohesin as well as CTCF (CCCTC-binding factor) in circadian rhythm. Using circular chromosome conformation capture sequencing, we systematically examined the interacting loci of a Bmal1-bound super-enhancer upstream of a clock gene Nr1d1 in mouse liver...
May 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27103456/characterization-of-a-cluster-of-ctcf-binding-sites-in-a-protocadherin-regulatory-region
#20
Zhai Yanan, Xu Quan, Guo Ya, Wu Qiang
The mammalian clustered protocadherin (Pcdh) locus contains more than 50 highly-similar genes arrayed in tandem. These Pcdh genes are organized into three closely-linked clusters (Pcdhα, Pcdhβ, and Pcdhγ). The encoded PCDH proteins play critical roles in neuronal diversity, single cell identity, and synaptic connectivity. Recent studies revealed that directional CTCF (CCCTC-binding factor) binding to CBS (CTCF-binding site) determines the specific interaction between enhancers and promoters, and the three Pcdhβγ clusters form two CCDs (CTCF/cohesin- mediated chromatin domain) which is important for gene regulation...
April 2016: Yi Chuan, Hereditas
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