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https://www.readbyqxmd.com/read/27803161/molecular-basis-for-cohesin-acetylation-by-establishment-of-sister-chromatid-cohesion-n-acetyltransferase-esco1
#1
Yadilette Rivera-Colón, Andrew Maguire, Glen P Liszczak, Adam S Olia, Ronen Marmorstein
Protein acetylation is a prevalent posttranslational modification that is regulated by diverse acetyltransferase enzymes. While histone acetyltransferases (HATs) have been well characterized both structurally and mechanistically, far less is known about non-histone acetyltransferase enzymes. The human ESCO1 and ESCO2 paralogs acetylate the cohesin complex subunit SMC3 to regulate the separation of sister chromatids during mitosis and meiosis. Missense mutations within the acetyltransferase domain of these proteins correlate with diseases, including endometrial cancers and Roberts Syndrome...
November 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27784745/mutational-landscape-and-gene-expression-patterns-in-adult-acute-myeloid-leukemias-with-monosomy-7-as-a-sole-abnormality
#2
Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Krzysztof Mrozek, Stefano Volinia, James S Blachly, Deedra Nicolet, Christopher Oakes, Karl Kroll, Shelley Orwick, Andrew J Carroll, Richard M Stone, John C Byrd, Albert de la Chapelle, Clara D Bloomfield
Monosomy of chromosome 7 is the most frequent autosomal monosomy in acute myeloid leukemia (AML), where it associates with poor clinical outcomes. However, molecular features associated with this sole monosomy subtype (-7 AML) which may give insights into the basis for its poor prognosis have not been characterized. In this study, we analyzed 36 cases of -7 AML for mutations in 81 leukemia/cancer-associated genes using a customized targeted next-generation sequencing panel (Miseq). Global gene and microRNA expression profiles were also determined using paired RNA and small RNA sequencing data...
October 26, 2016: Cancer Research
https://www.readbyqxmd.com/read/27742736/cohesin-mutations-in-cancer
#3
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/27739523/foxa-and-master-transcription-factors-recruit-mediator-and-cohesin-to-the-core-transcriptional-regulatory-circuitry-of-cancer-cells
#4
Michèle Fournier, Gaëlle Bourriquen, Fabien C Lamaze, Maxime C Côté, Éric Fournier, Charles Joly-Beauparlant, Vicky Caron, Stéphane Gobeil, Arnaud Droit, Steve Bilodeau
Controlling the transcriptional program is essential to maintain the identity and the biological functions of a cell. The Mediator and Cohesin complexes have been established as central cofactors controlling the transcriptional program in normal cells. However, the distribution, recruitment and importance of these complexes in cancer cells have not been fully investigated. Here we show that FOXA and master transcription factors are part of the core transcriptional regulatory circuitry of cancer cells and are essential to recruit M ediator and Cohesin...
October 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27669308/making-sense-of-the-tangle-insights-into-chromatin-folding-and-gene-regulation
#5
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
#6
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/27543316/mutations-of-myelodysplastic-syndromes-mds-an-update
#7
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/27466323/dynamic-cohesin-mediated-chromatin-architecture-controls-epithelial-mesenchymal-plasticity-in-cancer
#8
Jiyeon Yun, Sang-Hyun Song, Hwang-Phill Kim, Sae-Won Han, Eugene C Yi, Tae-You Kim
Epithelial to mesenchymal transition (EMT) and mesenchymal to epithelial transition (MET) are important interconnected events in tumorigenesis controlled by complex genetic networks. However, the cues that activate EMT-initiating factors and the mechanisms that reversibly connect EMT/MET are not well understood. Here, we show that cohesin-mediated chromatin organization coordinates EMT/MET by regulating mesenchymal genes. We report that RAD21, a subunit of the cohesin complex, is expressed in epithelial breast cancer cells, whereas its expression is decreased in mesenchymal cancer...
September 2016: EMBO Reports
https://www.readbyqxmd.com/read/27384851/clonal-evolution-in-myelodysplastic-syndromes
#9
Kenichi Yoshida
During the past ten years, genome-wide analysis of genetic alterations in myelodysplastic syndromes (MDS) has improved our understanding of their pathogenesis. Especially, single nucleotide polymorphism array karyotyping and next-generation sequencing technologies (NGS) have unveiled frequent genetic changes in novel functional pathways, including DNA methylation, RNA splicing and cohesin complex formation, in MDS. Moreover, NGS shed light on the clonal evolution which occurs during the development and progression of MDS, pre-cancerous lesions of MDS, and the effects of germline mutations in MDS...
June 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27291393/unusual-association-of-non-anaplastic-wilms-tumor-and-cornelia-de-lange-syndrome-case-report
#10
Claudia Santoro, Andrea Apicella, Fiorina Casale, Angela La Manna, Martina Di Martino, Daniela Di Pinto, Cristiana Indolfi, Silverio Perrotta
BACKGROUND: Cornelia de Lange syndrome is the prototype for cohesinopathy disorders, which are characterized by defects in chromosome segregation. Kidney malformations, including nephrogenic rests, are common in Cornelia de Lange syndrome. Only one post-mortem case report has described an association between Wilms tumor and Cornelia de Lange syndrome. Here, we describe the first case of a living child with both diseases. CASE PRESENTATION: Non-anaplastic triphasic nephroblastoma was diagnosed in a patient carrying a not yet reported mutation in NIPBL (c...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27207471/cohesin-mutations-in-human-cancer
#11
REVIEW
Victoria K Hill, Jung-Sik Kim, Todd Waldman
Cohesin is a highly-conserved protein complex that plays important roles in sister chromatid cohesion, chromatin structure, gene expression, and DNA repair. In humans, cohesin is a ubiquitously expressed, multi-subunit protein complex composed of core subunits SMC1A, SMC3, RAD21, STAG1/2 and regulatory subunits WAPL, PDS5A/B, CDCA5, NIPBL, and MAU2. Recent studies have demonstrated that genes encoding cohesin subunits are somatically mutated in a wide range of human cancers. STAG2 is the most commonly mutated subunit, and in a recent analysis was identified as one of only 12 genes that are significantly mutated in four or more cancer types...
August 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27091086/genome-stability-what-we-have-learned-from-cohesinopathies
#12
REVIEW
Francesco Cucco, Antonio Musio
Cohesin is a multiprotein complex involved in many DNA-related processes such as proper chromosome segregation, replication, transcription, and repair. Mutations in cohesin gene pathways are responsible for human diseases, collectively referred to as cohesinopathies. In addition, both cohesin gene expression dysregulation and mutations have been identified in cancer. Cohesinopathy cells are characterized by genome instability (GIN) visualized by a constellation of markers such as chromosome aneuploidies, chromosome aberrations, precocious sister chromatid separation, premature centromere separation, micronuclei formation, and sensitivity to genotoxic drugs...
June 2016: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/27072133/hdac8-inhibition-blocks-smc3-deacetylation-and-delays-cell-cycle-progression-without-affecting-cohesin-dependent-transcription-in-mcf7-cancer-cells
#13
Tanushree Dasgupta, Jisha Antony, Antony W Braithwaite, Julia A Horsfield
Cohesin, a multi-subunit protein complex involved in chromosome organization, is frequently mutated or aberrantly expressed in cancer. Multiple functions of cohesin, including cell division and gene expression, highlight its potential as a novel therapeutic target. The SMC3 subunit of cohesin is acetylated (ac) during S phase to establish cohesion between replicated chromosomes. Following anaphase, ac-SMC3 is deacetylated by HDAC8. Reversal of SMC3 acetylation is imperative for recycling cohesin so that it can be reloaded in interphase for both non-mitotic and mitotic functions...
June 10, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26871722/intact-cohesion-anaphase-and-chromosome-segregation-in-human-cells-harboring-tumor-derived-mutations-in-stag2
#14
Jung-Sik Kim, Xiaoyuan He, Bernardo Orr, Gordana Wutz, Victoria Hill, Jan-Michael Peters, Duane A Compton, Todd Waldman
Somatic mutations of the cohesin complex subunit STAG2 are present in diverse tumor types. We and others have shown that STAG2 inactivation can lead to loss of sister chromatid cohesion and alterations in chromosome copy number in experimental systems. However, studies of naturally occurring human tumors have demonstrated little, if any, correlation between STAG2 mutational status and aneuploidy, and have further shown that STAG2-deficient tumors are often euploid. In an effort to provide insight into these discrepancies, here we analyze the effect of tumor-derived STAG2 mutations on the protein composition of cohesin and the expected mitotic phenotypes of STAG2 mutation...
February 2016: PLoS Genetics
https://www.readbyqxmd.com/read/26838030/complete-loss-of-stag2-expression-is-an-indicator-of-good-prognosis-in-patients-with-bladder-cancer
#15
Yan Qiao, Xi Zhu, Aiwei Li, Shuo Yang, Jie Zhang
Stromal antigen 2 (STAG2) is an important member of cohesin, a conserved complex holding the sister chromatid together. Recent whole-genome sequencing studies have identified that genetic alterations of stag2 are common in bladder cancer (BC). The prognostic implications of STAG2 expression in BC remain unclear; we therefore analyzed its associations with the histopathological characteristics and clinical outcome in a Chinese population. We used immunohistochemistry assay to determine STAG2 protein expression in tumor tissues from 125 BC patients...
August 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/26821365/gene-regulation-and-chromatin-organization-relevance-of-cohesin-mutations-to-human-disease
#16
REVIEW
Erwan Watrin, Frank J Kaiser, Kerstin S Wendt
Consistent with the diverse roles of the cohesin complex in chromosome biology, mutations in genes encoding cohesin and its regulators are found in different types of cancer and in developmental disorders such as Cornelia de Lange Syndrome. It is so far considered that the defects caused by these mutations result from altered function of cohesin in regulating gene expression during development. Chromatin conformation analyses have established the importance of cohesin for the architecture of developmental gene clusters and in vivo studies in mouse and zebrafish demonstrated how cohesin defects lead to gene misregulation and to malformations similar to the related human syndromes...
April 2016: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/26783066/quantitative-phosphoproteomics-reveals-genistein-as-a-modulator-of-cell-cycle-and-dna-damage-response-pathways-in-triple-negative-breast-cancer-cells
#17
Yi Fang, Qian Zhang, Xin Wang, Xue Yang, Xiangyu Wang, Zhen Huang, Yuchen Jiao, Jing Wang
Around one sixth of breast cancer cases are classified as triple-negative breast cancer (TNBC), named after the absence of the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2); however, patients with TNBC suffer from poor clinical outcome and shortage of targeted therapy. Genistein, an estrogenic soy isoflavone, shows anticancer effects in TNBC cells such as inducing G2/M cell cycle arrest and apoptosis. However, the underlying mechanism of its anticancer effects is poorly understood and its elucidation can help the development of novel therapeutic strategies for TNBC...
March 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/26637939/leukemogenic-activity-of-cohesin-rings-true
#18
Mark S Williams, Tim C P Somervaille
Cohesin complex components are frequently mutated in human myeloid cancers. Three new studies now show that cohesin mutations disrupt the differentiation of normal hematopoietic stem and progenitor cells and enhance self-renewal, shedding light on how these alterations may contribute to leukemic transformation.
December 3, 2015: Cell Stem Cell
https://www.readbyqxmd.com/read/26637483/downregulation-of-smc1a-inhibits-growth-and-increases-apoptosis-and-chemosensitivity-of-colorectal-cancer-cells
#19
Jin Li, Wanting Feng, Longbang Chen, Jingdong He
OBJECTIVE: The structural maintenance of chromosomes (SMC) 1A protein is a component of the cohesin multiprotein complex that is essential for sister chromatid cohesion. SMC1A gene mutations have been reported in colorectal cancer. This study aimed to investigate the role of SMC1A gene expression in colorectal cancer in vitro. METHODS: SMC1A gene expression was silenced by lentivirus-mediated infection with small interfering RNA (siRNA) in the human colorectal cancer cell line HT-29...
February 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/26447899/the-expression-of-cohesin-subunit-sa2-predicts-breast-cancer-survival
#20
Heli Repo, Eliisa Löyttyniemi, Marjukka Nykänen, Minnamaija Lintunen, Henna Karra, Reino Pitkänen, Mirva Söderström, Teijo Kuopio, Pauliina Kronqvist
Cohesin is one of the main regulators of sister chromatid separation during the metaphase/anaphase transition. It is a multiprotein complex consisting of 4 core subunits, one of those being the SA2 subunit. SA2 plays the final role in dismantling the cohesion complex from the sister chromatids and also functions in DNA double-strand break repair and gene regulation. There is increasing evidence regarding the involvement of both overexpression and underexpression of cohesin in cancer. Here, we present expression patterns of SA2 in different types of human breast tissue, and the prognostic analysis in the material from breast cancer patients with long-term follow-up...
October 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
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