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  • 1
    Publication Date: 2018-08-02
    Description: Purpose: Adjuvant tamoxifen treatment revolutionized the management of estrogen receptor (ER)–positive breast cancers to prevent cancer recurrence; however, drug resistance compromises its clinical efficacy. The mechanisms underlying tamoxifen resistance are not fully understood, and no robust biomarker is available to reliably predict those who will be resistant. Here, we study BQ323636.1, a novel splice variant of the NCOR2 gene, and evaluate its efficacy in predicting tamoxifen resistance in patients with breast cancer. Experimental Design: A monoclonal anti-BQ323636.1 antibody that specifically recognizes the unique epitope of this splice variant was generated for in vitro mechanistic studies and for in vivo analysis by immunohistochemistry on tissue microarrays of two independent cohorts of 358 patients with more than 10 years clinical follow-up data, who had ER-positive primary breast cancer and received adjuvant tamoxifen treatment. An orthotopic mouse model was also used. Results: Overexpression of BQ323636.1 conferred resistance to tamoxifen in both in vitro and in an orthotopic mouse model. Mechanistically, coimmunoprecipitation showed BQ323636.1 could bind to NCOR2 and inhibit the formation of corepressor complex for the suppression of ER signaling. Nuclear BQ3232636.1 overexpression in patients samples was significantly associated with tamoxifen resistance ( P = 1.79 x 10 –6 , sensitivity 52.9%, specificity 72.0%). In tamoxifen-treated patients, nuclear BQ323636.1 overexpression was significantly correlated with cancer metastasis and disease relapse. Nuclear BQ323636.1 was also significantly associated with poorer overall survival ( P = 1.13 x 10 –4 ) and disease-specific survival ( P = 4.02 x 10 –5 ). Conclusions: These findings demonstrate that BQ323636.1 can be a reliable biomarker to predict tamoxifen resistance in patients with ER-positive breast cancer. Clin Cancer Res; 24(15); 3681–91. ©2018 AACR . See related commentary by Jordan, p. 3480
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 2
    Publication Date: 2012-02-10
    Description: Cancer immunoediting is a process by which immune cells, particularly lymphocytes of the adaptive immune system, protect the host from the development of cancer and alter tumour progression by driving the outgrowth of tumour cells with decreased sensitivity to immune attack. Carcinogen-induced mouse models of cancer have shown that primary tumour susceptibility is thereby enhanced in immune-compromised mice, whereas the capacity for such tumours to grow after transplantation into wild-type mice is reduced. However, many questions about the process of cancer immunoediting remain unanswered, in part because of the known antigenic complexity and heterogeneity of carcinogen-induced tumours. Here we adapted a genetically engineered, autochthonous mouse model of sarcomagenesis to investigate the process of cancer immunoediting. This system allows us to monitor the onset and growth of immunogenic and non-immunogenic tumours induced in situ that harbour identical genetic and histopathological characteristics. By comparing the development of such tumours in immune-competent mice with their development in mice with broad immunodeficiency or specific antigenic tolerance, we show that recognition of tumour-specific antigens by lymphocytes is critical for immunoediting against sarcomas. Furthermore, primary sarcomas were edited to become less immunogenic through the selective outgrowth of cells that were able to escape T lymphocyte attack. Loss of tumour antigen expression or presentation on major histocompatibility complex I was necessary and sufficient for this immunoediting process to occur. These results highlight the importance of tumour-specific-antigen expression in immune surveillance, and potentially, immunotherapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288744/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288744/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DuPage, Michel -- Mazumdar, Claire -- Schmidt, Leah M -- Cheung, Ann F -- Jacks, Tyler -- 1 U54 CA126515-01/CA/NCI NIH HHS/ -- P30 CA014051/CA/NCI NIH HHS/ -- P30 CA014051-38/CA/NCI NIH HHS/ -- P30 CA014051-39/CA/NCI NIH HHS/ -- P30 CA014051-40/CA/NCI NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- U54 CA126515/CA/NCI NIH HHS/ -- U54 CA126515-01/CA/NCI NIH HHS/ -- U54 CA126515-02/CA/NCI NIH HHS/ -- U54 CA126515-03/CA/NCI NIH HHS/ -- U54 CA126515-04/CA/NCI NIH HHS/ -- U54 CA126515-05/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Feb 8;482(7385):405-9. doi: 10.1038/nature10803.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22318517" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Neoplasm/genetics/*immunology ; Disease Models, Animal ; *Gene Expression Regulation, Neoplastic ; HEK293 Cells ; Humans ; Immunologic Surveillance/*immunology ; Methylcholanthrene ; Mice ; Neoplasms/chemically induced/genetics/*immunology/pathology ; Phenotype ; Sarcoma/chemically induced/genetics/immunology/pathology ; T-Lymphocytes/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheung, Felix -- England -- Nature. 2014 Oct 30;514(7524):S60-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25368890" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*trends ; Biotechnology/*trends ; Breeding ; Crops, Agricultural/*genetics/*growth & development ; Food Supply ; Genes, Plant/genetics ; Genome, Plant/genetics ; Hybridization, Genetic ; Oryza/*genetics/*growth & development
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Nature Publishing Group (NPG)
    Publication Date: 2015-04-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dong-Yan, Jin -- Cheung, Felix -- England -- Nature. 2015 Apr 30;520(7549):S37. doi: 10.1038/520S37a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25924200" target="_blank"〉PubMed〈/a〉
    Keywords: Bibliometrics ; China ; Hong Kong ; *Internationality ; Peer Review, Research/*methods/*standards ; *Personnel Selection ; Research Personnel/*standards ; United States ; Universities
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2011-11-18
    Description: Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation. Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Myr ago). Papilionoids are the largest clade, dating nearly to the origin of legumes and containing most cultivated species. Medicago truncatula is a long-established model for the study of legume biology. Here we describe the draft sequence of the M. truncatula euchromatin based on a recently completed BAC assembly supplemented with Illumina shotgun sequence, together capturing approximately 94% of all M. truncatula genes. A whole-genome duplication (WGD) approximately 58 Myr ago had a major role in shaping the M. truncatula genome and thereby contributed to the evolution of endosymbiotic nitrogen fixation. Subsequent to the WGD, the M. truncatula genome experienced higher levels of rearrangement than two other sequenced legumes, Glycine max and Lotus japonicus. M. truncatula is a close relative of alfalfa (Medicago sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics. As such, the M. truncatula genome sequence provides significant opportunities to expand alfalfa's genomic toolbox.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272368/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272368/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Young, Nevin D -- Debelle, Frederic -- Oldroyd, Giles E D -- Geurts, Rene -- Cannon, Steven B -- Udvardi, Michael K -- Benedito, Vagner A -- Mayer, Klaus F X -- Gouzy, Jerome -- Schoof, Heiko -- Van de Peer, Yves -- Proost, Sebastian -- Cook, Douglas R -- Meyers, Blake C -- Spannagl, Manuel -- Cheung, Foo -- De Mita, Stephane -- Krishnakumar, Vivek -- Gundlach, Heidrun -- Zhou, Shiguo -- Mudge, Joann -- Bharti, Arvind K -- Murray, Jeremy D -- Naoumkina, Marina A -- Rosen, Benjamin -- Silverstein, Kevin A T -- Tang, Haibao -- Rombauts, Stephane -- Zhao, Patrick X -- Zhou, Peng -- Barbe, Valerie -- Bardou, Philippe -- Bechner, Michael -- Bellec, Arnaud -- Berger, Anne -- Berges, Helene -- Bidwell, Shelby -- Bisseling, Ton -- Choisne, Nathalie -- Couloux, Arnaud -- Denny, Roxanne -- Deshpande, Shweta -- Dai, Xinbin -- Doyle, Jeff J -- Dudez, Anne-Marie -- Farmer, Andrew D -- Fouteau, Stephanie -- Franken, Carolien -- Gibelin, Chrystel -- Gish, John -- Goldstein, Steven -- Gonzalez, Alvaro J -- Green, Pamela J -- Hallab, Asis -- Hartog, Marijke -- Hua, Axin -- Humphray, Sean J -- Jeong, Dong-Hoon -- Jing, Yi -- Jocker, Anika -- Kenton, Steve M -- Kim, Dong-Jin -- Klee, Kathrin -- Lai, Hongshing -- Lang, Chunting -- Lin, Shaoping -- Macmil, Simone L -- Magdelenat, Ghislaine -- Matthews, Lucy -- McCorrison, Jamison -- Monaghan, Erin L -- Mun, Jeong-Hwan -- Najar, Fares Z -- Nicholson, Christine -- Noirot, Celine -- O'Bleness, Majesta -- Paule, Charles R -- Poulain, Julie -- Prion, Florent -- Qin, Baifang -- Qu, Chunmei -- Retzel, Ernest F -- Riddle, Claire -- Sallet, Erika -- Samain, Sylvie -- Samson, Nicolas -- Sanders, Iryna -- Saurat, Olivier -- Scarpelli, Claude -- Schiex, Thomas -- Segurens, Beatrice -- Severin, Andrew J -- Sherrier, D Janine -- Shi, Ruihua -- Sims, Sarah -- Singer, Susan R -- Sinharoy, Senjuti -- Sterck, Lieven -- Viollet, Agnes -- Wang, Bing-Bing -- Wang, Keqin -- Wang, Mingyi -- Wang, Xiaohong -- Warfsmann, Jens -- Weissenbach, Jean -- White, Doug D -- White, Jim D -- Wiley, Graham B -- Wincker, Patrick -- Xing, Yanbo -- Yang, Limei -- Yao, Ziyun -- Ying, Fu -- Zhai, Jixian -- Zhou, Liping -- Zuber, Antoine -- Denarie, Jean -- Dixon, Richard A -- May, Gregory D -- Schwartz, David C -- Rogers, Jane -- Quetier, Francis -- Town, Christopher D -- Roe, Bruce A -- BB/G023832/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBS/B/11524/Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2011 Nov 16;480(7378):520-4. doi: 10.1038/nature10625.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Pathology, University of Minnesota, St Paul, Minnesota 55108, USA. neviny@umn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22089132" target="_blank"〉PubMed〈/a〉
    Keywords: *Biological Evolution ; *Genome, Plant ; Medicago truncatula/*genetics/*microbiology ; Molecular Sequence Data ; Nitrogen Fixation/genetics ; Rhizobium/*physiology ; Soybeans/genetics ; *Symbiosis ; Synteny ; Vitis/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Nature Publishing Group (NPG)
    Publication Date: 2011-12-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheung, Felix -- England -- Nature. 2011 Dec 21;480(7378):S94-5. doi: 10.1038/480S94a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22190091" target="_blank"〉PubMed〈/a〉
    Keywords: Acupuncture Therapy ; Back Pain/therapy ; China ; Hospitals ; Humans ; *Medicine, Chinese Traditional/economics/methods/standards
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2016-03-05
    Description: Gilbert et al. conclude that evidence from the Open Science Collaboration's Reproducibility Project: Psychology indicates high reproducibility, given the study methodology. Their very optimistic assessment is limited by statistical misconceptions and by causal inferences from selectively interpreted, correlational data. Using the Reproducibility Project: Psychology data, both optimistic and pessimistic conclusions about reproducibility are possible, and neither are yet warranted.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, Christopher J -- Bahnik, Stepan -- Barnett-Cowan, Michael -- Bosco, Frank A -- Chandler, Jesse -- Chartier, Christopher R -- Cheung, Felix -- Christopherson, Cody D -- Cordes, Andreas -- Cremata, Edward J -- Della Penna, Nicolas -- Estel, Vivien -- Fedor, Anna -- Fitneva, Stanka A -- Frank, Michael C -- Grange, James A -- Hartshorne, Joshua K -- Hasselman, Fred -- Henninger, Felix -- van der Hulst, Marije -- Jonas, Kai J -- Lai, Calvin K -- Levitan, Carmel A -- Miller, Jeremy K -- Moore, Katherine S -- Meixner, Johannes M -- Munafo, Marcus R -- Neijenhuijs, Koen I -- Nilsonne, Gustav -- Nosek, Brian A -- Plessow, Franziska -- Prenoveau, Jason M -- Ricker, Ashley A -- Schmidt, Kathleen -- Spies, Jeffrey R -- Stieger, Stefan -- Strohminger, Nina -- Sullivan, Gavin B -- van Aert, Robbie C M -- van Assen, Marcel A L M -- Vanpaemel, Wolf -- Vianello, Michelangelo -- Voracek, Martin -- Zuni, Kellylynn -- New York, N.Y. -- Science. 2016 Mar 4;351(6277):1037. doi: 10.1126/science.aad9163.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Russell Sage College, Troy, NY, USA. nosek@virginia.edu. ; University of Wurzburg, Wurzburg, Germany. ; University of Waterloo, Waterloo, Ontario, Canada. ; Virginia Commonwealth University, Richmond, VA, USA. ; University of Michigan, Ann Arbor, MI 48104, USA. Mathematica Policy Research, Washington, DC, USA. ; Ashland University, Ashland, OH, USA. ; Michigan State University, East Lansing, MI, USA. ; Southern Oregon University, Ashland, OR, USA. ; University of Gottingen, Institute for Psychology, Gottingen, Germany. ; University of Southern California, Los Angeles, CA, USA. ; Australian National University, Canberra, Australia. ; Technische Universitat Braunschweig, Braunschweig, Germany. ; Parmenides Stiftung, Munich, Germany. ; Queen's University, Kingston, Ontario, Canada. ; Stanford University, Stanford, CA, USA. ; Keele University, Keele, Staffordshire, UK. ; Boston College, Chestnut Hill, MA, USA. ; Radboud University Nijmegen, Nijmegen, Netherlands. ; University of Koblenz-Landau, Landau, Germany. ; Erasmus Medical Center, Rotterdam, Netherlands. ; University of Amsterdam, Amsterdam, Netherlands. ; Harvard University, Cambridge, MA, USA. ; Occidental College, Los Angeles, CA, USA. ; Willamette University, Salem, OR, USA. ; Arcadia University, Glenside, PA, USA. ; University of Potsdam, Potsdam, Germany. ; University of Bristol, Bristol, UK. ; Vrije Universiteit Amsterdam, Amsterdam, Netherlands. ; Karolinska Institutet, Stockholm University, Stockholm, Sweden. ; Center for Open Science, Charlottesville, VA, USA. University of Virginia, Charlottesville, VA, USA. nosek@virginia.edu. ; Harvard Medical School, Boston, MA, USA. ; Loyola University, Baltimore, MD, USA. ; University of California, Riverside, CA, USA. ; Wesleyan University, Middletown, CT, USA. ; Center for Open Science, Charlottesville, VA, USA. University of Virginia, Charlottesville, VA, USA. ; University of Konstanz, Konstanz, Germany. ; Yale University, New Haven, CT, USA. ; Coventry University, Coventry, UK. ; Tilburg University, Tilburg, Netherlands. ; Tilburg University, Tilburg, Netherlands. Utrecht University, Utrecht, Netherlands. ; University of Leuven, Leuven, Belgium. ; University of Padova, Padova, Italy. ; University of Vienna, Vienna, Austria. ; Adams State University, Alamosa, CO, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26941312" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2018-09-05
    Description: Despite advances in our understanding of the genetics of pancreatic ductal adenocarcinoma (PDAC), the efficacy of therapeutic regimens targeting aberrant signaling pathways remains highly limited. Therapeutic strategies are greatly hampered by the extensive desmoplasia that comprises heterogeneous cell populations. Notch signaling is a contentious pathway exerting opposite roles in tumorigenesis depending on cellular context. Advanced model systems are needed to gain more insights into complex signaling in the multilayered tumor microenvironment. In this study, we employed a dual recombinase-based in vivo strategy to modulate Notch signaling specifically in myeloid cells to dissect the tumorigenic role of Notch in PDAC stroma. Pancreas-specific KrasG12D activation and loss of Tp53 was induced using a Pdx1-Flp transgene, whereas Notch signaling was genetically targeted using a myeloid-targeting Lyz2-Cre strain for either activation of Notch2-IC or deletion of Rbpj. Myeloid-specific Notch activation significantly decreased tumor infiltration by protumorigenic M2 macrophages in spontaneous endogenous PDAC, which translated into significant survival benefit. Further characterization revealed upregulated antigen presentation and cytotoxic T effector phenotype upon Notch-induced M2 reduction. This approach is the first proof of concept for genetic targeting and reprogramming of myeloid cells in a complex disease model of PDAC and provides evidence for a regulatory role of Notch signaling in intratumoral immune phenotypes.Significance: This study provides insight into the role of myeloid-dependent NOTCH signaling in PDAC and accentuates the need to dissect differential roles of signaling pathways in different cellular components within the tumor microenvironment. Cancer Res; 78(17); 4997–5010. ©2018 AACR.
    Print ISSN: 0008-5472
    Electronic ISSN: 1538-7445
    Topics: Medicine
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  • 9
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    Nature Publishing Group (NPG)
    Publication Date: 2011-12-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheung, Felix -- England -- Nature. 2011 Dec 21;480(7378):S82-3. doi: 10.1038/480S82a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22190085" target="_blank"〉PubMed〈/a〉
    Keywords: History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; History, Medieval ; Humans ; *Medicine, Chinese Traditional/economics/history/standards/trends/utilization ; Research
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Keywords: human ; IN-VIVO ; MODEL ; MODELS ; DENSITY ; NEW-YORK ; DISTINCT ; GENOME ; microarray ; PROTEIN ; PROTEINS ; SACCHAROMYCES-CEREVISIAE ; RESOLUTION ; COMPLEX ; COMPLEXES ; DNA ; DOMAIN ; chromosome ; ALPHA ; CHROMATIN ; MICROARRAY DATA ; ASSAY ; microarrays ; genetics ; COMPONENT ; PCR ; REGION ; POLYMERASE-CHAIN-REACTION ; CHAIN-REACTION ; ORGANIZATION ; CHROMATIN STRUCTURE ; heredity ; DOMAINS ; LOCATION ; CHAIN ; VARIANT ; polymerase chain reaction ; LEVEL ; analysis ; ASSAYS ; USA ; genomic ; microbiology ; ALPHA-SATELLITE DNA ; FUNCTIONAL HUMAN CENTROMERE ; INNER KINETOCHORE PLATE ; NULL MICE ; RICE CENTROMERE
    Abstract: Background: Mammalian centromere formation is dependent on chromatin that contains centromere protein ( CENP)-A, which is the centromere-specific histone H3 variant. Human neocentromeres have acquired CENP-A chromatin epigenetically in ectopic chromosomal locations on low-copy complex DNA. Neocentromeres permit detailed investigation of centromeric chromatin organization that is not possible in the highly repetitive alpha satellite DNA present at endogenous centromeres. Results: We have examined the distribution of CENP-A, as well as two additional centromeric chromatin-associated proteins ( CENP-C and CENP-H), across neocentromeric DNA using chromatin immunoprecipitation ( ChIP) on CHIP assays on custom genomic microarrays at three different resolutions. Analysis of two neocentromeres using a contiguous bacterial artificial chromosome ( BAC) microarray spanning bands 13q31.3 to 13q33.1 shows that both CENP-C and CENP-H co-localize to the CENP-A chromatin domain. Using a higher resolution polymerase chain reaction ( PCR)-amplicon microarray spanning the neocentromere, we find that the CENP-A chromatin is discontinuous, consisting of a major domain of about 87.8 kilobases ( kb) and a minor domain of about 13.2 kb, separated by an approximately 158 kb region devoid of CENPs. Both CENP-A domains exhibit co-localization of CENP-C and CENP-H, defining a distinct inner kinetochore chromatin structure that is consistent with higher order chromatin looping models at centromeres. The PCR microarray data suggested varying density of CENP-A nucleosomes across the major domain, which was confirmed using a higher resolution oligo-based microarray. Conclusion: Centromeric chromatin consists of several CENP-A subdomains with highly discontinuous CENP-A chromatin at both the level of individual nucleosomes and at higher order chromatin levels, raising questions regarding the overall structure of centromeric chromatin
    Type of Publication: Journal article published
    PubMed ID: 17651496
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