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Philipp Bergmaier, Oliver Weth, Sven Dienstbach, Thomas Boettger, Niels Galjart, Marco Mernberger, Marek Bartkuhn, Rainer Renkawitz
The two paralogous zinc finger factors CTCF and CTCFL differ in expression such that CTCF is ubiquitously expressed, whereas CTCFL is found during spermatogenesis and in some cancer types in addition to other cell types. Both factors share the highly conserved DNA binding domain and are bound to DNA sequences with an identical consensus. In contrast, both factors differ substantially in the number of bound sites in the genome. Here, we addressed the molecular features for this binding specificity. In contrast to CTCF we found CTCFL highly enriched at 'open' chromatin marked by H3K27 acetylation, H3K4 di- and trimethylation, H3K79 dimethylation and H3K9 acetylation plus the histone variant H2A...
May 31, 2018: Nucleic Acids Research
Kamel Jabbari, Peter Heger, Ranu Sharma, Thomas Wiehe
The CCCTC-binding factor (CTCF) is multi-functional, ubiquitously expressed, and highly conserved from Drosophila to human. It has important roles in transcriptional insulation and the formation of a high-dimensional chromatin structure. CTCF has a paralog called "Brother of Regulator of Imprinted Sites" (BORIS) or "CTCF-like" (CTCFL). It binds DNA at sites similar to those of CTCF. However, the expression profiles of the two proteins are quite different. We investigated the evolutionary trajectories of the two proteins after the duplication event using a phylogenomic and interactomic approach...
January 30, 2018: Life
Nicolas Altemose, Nudrat Noor, Emmanuelle Bitoun, Afidalina Tumian, Michael Imbeault, J Ross Chapman, A Radu Aricescu, Simon R Myers
PRDM9 binding localizes almost all meiotic recombination sites in humans and mice. However, most PRDM9-bound loci do not become recombination hotspots. To explore factors that affect binding and subsequent recombination outcomes, we mapped human PRDM9 binding sites in a transfected human cell line and measured PRDM9-induced histone modifications. These data reveal varied DNA-binding modalities of PRDM9. We also find that human PRDM9 frequently binds promoters, despite their low recombination rates, and it can activate expression of a small number of genes including CTCFL and VCX ...
October 26, 2017: ELife
Mitsutaka Kadota, Yuichiro Hara, Kaori Tanaka, Wataru Takagi, Chiharu Tanegashima, Osamu Nishimura, Shigehiro Kuraku
The nuclear protein CCCTC-binding factor (CTCF) contributes as an insulator to chromatin organization in animal genomes. Currently, our knowledge of its binding property is confined mainly to mammals. In this study, we identified CTCF homologs in extant jawless fishes and performed ChIP-seq for the CTCF protein in the Arctic lamprey. Our phylogenetic analysis suggests that the lamprey lineage experienced gene duplication that gave rise to its unique paralog, designated CTCF2, which is independent from the previously recognized duplication between CTCF and CTCFL...
July 10, 2017: Scientific Reports
Christine Légaré, Ayodélé Akintayo, Patrick Blondin, Ezequiel Calvo, Robert Sullivan
STUDY QUESTION: Can region-specific transcriptional profiling of the epididymis from fertile and sub-fertile bulls predict the etiology of fertility/sub-fertility in males? SUMMARY ANSWER: The highly regulated gene expression along the bovine epididymis is affected by the fertility status of bulls used for artificial insemination. WHAT IS KNOWN ALREADY: In mammals, sperm maturation and storage occur in the epididymis. Each epididymal segment has his own transcriptomic signature that modulates the intraluminal composition and consequently governs sequential modifications of the maturing male gamete...
June 1, 2017: Molecular Human Reproduction
Aurélie Van Tongelen, Axelle Loriot, Charles De Smet
Global loss of DNA methylation is frequently observed in the genome of human tumors. Although this epigenetic alteration is clearly associated with cancer progression, the way it exerts its pro-tumoral effect remains incompletely understood. A remarkable consequence of DNA hypomethylation in tumors is the aberrant activation of "cancer-germline" genes (also known as "cancer-testis" genes), which comprise a diverse group of germline-specific genes that use DNA methylation as a primary mechanism for repression in normal somatic tissues...
June 28, 2017: Cancer Letters
Koteswara Rao Garikapati, Nibedita Patel, Venkata Krishna Kanth Makani, Priyanka Cilamkoti, Utpal Bhadra, Manika Pal Bhadra
BORIS/CTCFL is a vital nucleotide binding protein expressed during embryogenesis and gametogenesis. BORIS/CTCFL is the paralogue of transcriptional repressor protein CTCF, which is aberrantly expressed in various malignancies and primarily re-expressed in cancer stem cells (CSCs). The mechanism behind regulation of BORIS in various cancer conditions and tumor metastases is so far not explored in detail. The aim of the study was to understand the influence of BORIS/CTCFL on stemness and metastasis by regulating well-known oncogenes and related signaling pathways...
February 26, 2017: Biochemical and Biophysical Research Communications
Yonatan Herzig, Shir Nevo, Chamutal Bornstein, Miriam R Brezis, Sharon Ben-Hur, Aya Shkedy, Michal Eisenberg-Bord, Ben Levi, Michael Delacher, Yael Goldfarb, Eyal David, Leehee Weinberger, Sergey Viukov, Shifra Ben-Dor, Matthieu Giraud, Jacob H Hanna, Achim Breiling, Frank Lyko, Ido Amit, Markus Feuerer, Jakub Abramson
Aire is a transcriptional regulator that induces promiscuous expression of thousands of genes encoding tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). While the target genes of Aire are well characterized, the transcriptional programs that regulate its own expression have remained elusive. Here we comprehensively analyzed both cis-acting and trans-acting regulatory mechanisms and found that the Aire locus was insulated by the global chromatin organizer CTCF and was hypermethylated in cells and tissues that did not express Aire...
February 2017: Nature Immunology
Elena M Pugacheva, Evgeny Teplyakov, Qiongfang Wu, Jingjing Li, Cheng Chen, Chengcheng Meng, Jian Liu, Susan Robinson, Dmitry Loukinov, Abdelhalim Boukaba, Andrew Paul Hutchins, Victor Lobanenkov, Alexander Strunnikov
BACKGROUND: A common aberration in cancer is the activation of germline-specific proteins. The DNA-binding proteins among them could generate novel chromatin states, not found in normal cells. The germline-specific transcription factor BORIS/CTCFL, a paralog of chromatin architecture protein CTCF, is often erroneously activated in cancers and rewires the epigenome for the germline-like transcription program. Another common feature of malignancies is the changed expression and epigenetic states of genomic repeats, which could alter the transcription of neighboring genes and cause somatic mutations upon transposition...
2016: Epigenetics & Chromatin
Se-Lyun Yoon, Yun-Gil Roh, In-Sun Chu, Jeonghoon Heo, Seung Il Kim, Heekyung Chang, Tae-Hong Kang, Jin Woong Chung, Sang Seok Koh, Vladimir Larionov, Sun-Hee Leem
Aberrant expression of BORIS/CTCFL (Brother of the Regulator of Imprinted Sites/CTCF-like protein) is reported in different malignancies. In this study, we characterized the entire promoter region of BORIS/CTCFL, including the CpG islands, to assess the relationship between BORIS expression and lung cancer. To simplify the construction of luciferase reporter cassettes with various-sized portions of the upstream region, genomic copies of BORIS were isolated using TAR cloning technology. We analyzed three promoter blocks: the GATA/CCAAT box, the CpG islands and the minisatellite region BORIS-MS2...
July 15, 2016: Experimental & Molecular Medicine
Takuya Asano, Yoshihiko Hirohashi, Toshihiko Torigoe, Tasuku Mariya, Ryota Horibe, Takafumi Kuroda, Yuta Tabuchi, Hiroshi Saijo, Kazuyo Yasuda, Masahito Mizuuchi, Akari Takahashi, Hiroko Asanuma, Tadashi Hasegawa, Tsuyoshi Saito, Noriyuki Sato
Cervical cancer is a major cause of cancer death in females worldwide. Cervical cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are resistant to conventional radiotherapy and chemotherapy, and CSCs/CICs are thought to be responsible for recurrence. Eradication of CSCs/CICs is thus essential to cure cervical cancer. In this study, we isolated cervical CSCs/CICs by sphere culture, and we identified a cancer testis (CT) antigen, CTCFL/BORIS, that is expressed in cervical CSCs/CICs. BORIS has 23 mRNA isoform variants classified by 6 subfamilies (sfs), and they encode 17 different BORIS peptides...
March 8, 2016: Oncotarget
Elena M Pugacheva, Samuel Rivero-Hinojosa, Celso A Espinoza, Claudia Fabiola Méndez-Catalá, Sungyun Kang, Teruhiko Suzuki, Natsuki Kosaka-Suzuki, Susan Robinson, Vijayaraj Nagarajan, Zhen Ye, Abdelhalim Boukaba, John E J Rasko, Alexander V Strunnikov, Dmitri Loukinov, Bing Ren, Victor V Lobanenkov
BACKGROUND: CTCF and BORIS (CTCFL), two paralogous mammalian proteins sharing nearly identical DNA binding domains, are thought to function in a mutually exclusive manner in DNA binding and transcriptional regulation. RESULTS: Here we show that these two proteins co-occupy a specific subset of regulatory elements consisting of clustered CTCF binding motifs (termed 2xCTSes). BORIS occupancy at 2xCTSes is largely invariant in BORIS-positive cancer cells, with the genomic pattern recapitulating the germline-specific BORIS binding to chromatin...
2015: Genome Biology
Loredana Alberti, Lorena Losi, Serge Leyvraz, Jean Benhattar
Cancer stem cells are cancer cells characterized by stem cell properties and represent a small population of tumor cells that drives tumor development, progression, metastasis and drug resistance. To date, the molecular mechanisms that generate and regulate cancer stem cells are not well defined. BORIS (Brother of Regulator of Imprinted Sites) or CTCFL (CTCF-like) is a DNA-binding protein that is expressed in normal tissues only in germ cells and is re-activated in tumors. Recent evidences have highlighted the correlation of BORIS/CTCFL expression with poor overall survival of different cancer patients...
2015: PloS One
Leyla Sati, Caroline Zeiss, Krishna Yekkala, Ramazan Demir, James McGrath
CTCFL, a paralog of CTCF, also known as BORIS (brother of regulator of imprinted sites), is a testis-expressed gene whose function is largely unknown. Its product is a cancer testis antigen (CTA), and it is often expressed in tumor cells and also seen in two benign human vascular malformations, juvenile angiofibromas and infantile hemangiomas. To understand the function of Ctcfl, we created tetracycline-inducible Ctcfl transgenic mice. We show that Ctcfl expression during embryogenesis results in growth retardation, eye malformations, multiorgan pathologies, vascular defects, and neonatal death...
October 2015: Molecular and Cellular Biology
Oliver Weth, Christine Paprotka, Katharina Günther, Astrid Schulte, Manuel Baierl, Joerg Leers, Niels Galjart, Rainer Renkawitz
Insulators functionally separate active chromatin domains from inactive ones. The insulator factor, CTCF, has been found to bind to boundaries and to mediate insulator function. CTCF binding sites are depleted for the histone modification H3K27me3 and are enriched for the histone variant H3.3. In order to determine whether demethylation of H3K27me3 and H3.3 incorporation are a requirement for CTCF binding at domain boundaries or whether CTCF causes these changes, we made use of the LacI DNA binding domain to control CTCF binding by the Lac inducer IPTG...
October 29, 2014: Nucleic Acids Research
Loredana Alberti, Stéphanie Renaud, Lorena Losi, Serge Leyvraz, Jean Benhattar
BORIS/CTCFL is a member of cancer testis antigen family normally expressed in germ cells. In tumors, it is aberrantly expressed although its functions are not completely well-defined. To better understand the functions of BORIS in cancer, we selected the embryonic cancer cells as a model. Using a molecular beacon, which specifically targets BORIS mRNA, we demonstrated that BORIS positive cells are a small subpopulation of tumor cells (3-5% of total). The BORIS-positive cells isolated using BORIS-molecular beacon, expressed higher telomerase hTERT, stem cell (NANOG, OCT4, SOX2) and cancer stem cell marker genes (CD44 and ALDH1) compared to the BORIS-negative tumor cells...
2014: PloS One
Graciela Zambrano-Galván, Miguel Reyes-Romero, Ronell Bologna-Molina, Oscar Eduardo Almeda-Ojeda, Obed Lemus-Rojero
Peripheral giant cell granuloma (PGCG) is a relatively common benign reactive lesion of the oral cavity which can occur at any age. CTCFL/BORIS (CTCF like/Brother of the Regulator of Imprinted Sites) and CTCF (CCCTC-binding factor) are paralogous genes with an important role in the regulation of gene expression, genomic imprinting, and nuclear chromatin insulators regulation. BORIS expression promotes cell immortalization and growth while CTCF has tumor suppressor activity; the expression pattern may reflect the reverse transcription silencing of BORIS...
2014: Case Reports in Dentistry
Michele Zampieri, Fabio Ciccarone, Rocco Palermo, Samantha Cialfi, Claudio Passananti, Sabina Chiaretti, Daniela Nocchia, Claudio Talora, Isabella Screpanti, Paola Caiafa
Aberrant upregulation of NOTCH3 gene plays a critical role in cancer pathogenesis. However, the underlying mechanisms are still unknown. We tested here the hypothesis that aberrant epigenetic modifications in the NOTCH3 promoter region might account for its upregulation in cancer cells. We compared DNA and histone methylation status of NOTCH3 promoter region in human normal blood cells and T cell acute lymphoblastic leukemia (T-ALL) cell lines, differentially expressing NOTCH3. We found that histone methylation, rather than DNA hypomethylation, contributes towards establishing an active chromatin status of NOTCH3 promoter in NOTCH3 overexpressing cancer cells...
September 2014: Biochimica et Biophysica Acta
Sara Soltanian, Hesam Dehghani, Maryam M Matin, Ahmad Reza Bahrami
BORIS/CTCFL is an 11 zinc finger protein, which is the paralog of CTCF, a ubiquitously expressed protein with diverse roles in gene expression and chromatin organization. Several studies have shown that the expression of BORIS is restricted to normal adult testis, pluripotent cells, and diverse cancer cell lines. Thus, it is known as a cancer-testis (CT) gene that has been hypothesized to exhibit oncogenic properties and to be involved in cancer cell proliferation. On the contrary, other reports have shown that its expression is more widespread and can be detected in differentiated and normal somatic cells; hence, it might have roles in general cellular functions...
August 2014: Acta Biochimica et Biophysica Sinica
Erling A Hoivik, Kanthida Kusonmano, Mari K Halle, Anna Berg, Elisabeth Wik, Henrica M J Werner, Kjell Petersen, Anne M Oyan, Karl-Henning Kalland, Camilla Krakstad, Jone Trovik, Martin Widschwendter, Helga B Salvesen
Cancers arise through accumulating genetic and epigenetic alterations, considered relevant for phenotype and approaches to targeting new therapies. We investigated a unique collection of endometrial cancer precursor samples and clinically annotated primary and metastatic lesions for two evolutionary and functionally related transcription factors, CCCTC-binding factor (zinc finger protein) (CTCF) and its paralogue CTCF-like factor, also denoted Brother of the Regulator of Imprinted Sites (CTCFL/BORIS). CTCF, a chromatin modeling- and transcription factor, is normally expressed in a ubiquitous fashion, while CTCFL/BORIS is restricted to the testis...
February 28, 2014: Oncotarget
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