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Ctcf cohesin

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...
October 14, 2016: Cold Spring Harbor Perspectives in Medicine
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
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
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
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
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
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
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
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
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
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
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
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
Matthias Merkenschlager, Elphège P Nora
Genome function, replication, integrity, and propagation rely on the dynamic structural organization of chromosomes during the cell cycle. Genome folding in interphase provides regulatory segmentation for appropriate transcriptional control, facilitates ordered genome replication, and contributes to genome integrity by limiting illegitimate recombination. Here, we review recent high-resolution chromosome conformation capture and functional studies that have informed models of the spatial and regulatory compartmentalization of mammalian genomes, and discuss mechanistic models for how CTCF and cohesin control the functional architecture of mammalian chromosomes...
August 31, 2016: Annual Review of Genomics and Human Genetics
Cary Stelloh, Michael H Reimer, Kirthi Pulakanti, Steven Blinka, Jonathan Peterson, Luca Pinello, Shuang Jia, Sergei Roumiantsev, Martin J Hessner, Samuel Milanovich, Guo-Cheng Yuan, Sridhar Rao
BACKGROUND: The cohesin complex consists of multiple core subunits that play critical roles in mitosis and transcriptional regulation. The cohesin-associated protein Wapal plays a central role in off-loading cohesin to facilitate sister chromatid separation, but its role in regulating mammalian gene expression is not understood. We used embryonic stem cells as a model, given that the well-defined transcriptional regulatory circuits were established through master transcription factors and epigenetic pathways that regulate their ability to maintain a pluripotent state...
2016: Epigenetics & Chromatin
Rodolfo Ghirlando, Gary Felsenfeld
The role of the zinc finger protein CTCF in organizing the genome within the nucleus is now well established. Widely separated sites on DNA, occupied by both CTCF and the cohesin complex, make physical contacts that create large loop domains. Additional contacts between loci within those domains, often also mediated by CTCF, tend to be favored over contacts between loci in different domains. A large number of studies during the past 2 years have addressed the questions: How are these loops generated? What are the effects of disrupting them? Are there rules governing large-scale genome organization? It now appears that the strongest and evolutionarily most conserved of these CTCF interactions have specific rules for the orientation of the paired CTCF sites, implying the existence of a nonequilibrium mechanism of generation...
April 15, 2016: Genes & Development
Joo-Hong Park, Yeeun Choi, Min-Ji Song, Keunhee Park, Jong-Joo Lee, Hyoung-Pyo Kim
IL-21, a pleiotropic cytokine strongly linked with autoimmunity and inflammation, regulates diverse immune responses. IL-21 can be potently induced in CD4(+) T cells by IL-6; however, very little is known about the mechanisms underlying the transcriptional regulation of the Il21 gene at the chromatin level. In this study, we demonstrated that a conserved noncoding sequence located 49 kb upstream of the Il21 gene contains an enhancer element that can upregulate Il21 gene expression in a STAT3- and NFAT-dependent manner...
May 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Tamer Ali, Rainer Renkawitz, Marek Bartkuhn
The genomic organization into active and inactive chromatin domains imposes specific requirements for having domain boundaries to prohibit interference between the opposing activities of neighbouring domains. These boundaries provide an insulator function by binding architectural proteins that mediate long-range interactions. Among these, CTCF plays a prominent role in establishing chromatin loops (between pairs of CTCF binding sites) through recruiting cohesin. CTCF-mediated long-range interactions are integral for a multitude of topological features of interphase chromatin, such as the formation of topologically associated domains, domain insulation, enhancer blocking and even enhancer function...
April 2016: Current Opinion in Genetics & Development
Giorgio Bernardi
How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes, and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The solution to this question presented here rests on the correlations that were found to hold between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase. The key points are the following: (1) The transition from the looped domains and subdomains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through their unfolding into an extended chromatin structure (probably a 10-nm "beads-on-a-string" structure); (2) the architectural proteins of interphase chromatin, such as CTCF and cohesin subunits, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; and (3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the reversibility of the interphase to mitosis process and the "mitotic memory" of interphase architecture...
2015: Cold Spring Harbor Symposia on Quantitative Biology
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pcbi.1003877.].
January 2016: PLoS Computational Biology
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