{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:21:21Z","timestamp":1759335681999,"version":"3.37.3"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,1,29]],"date-time":"2015-01-29T00:00:00Z","timestamp":1422489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"FAPERJ-Brazil"},{"name":"CAPES-COFECUB"},{"DOI":"10.13039\/501100006702","name":"Universidade do Estado do Rio de Janeiro","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006702","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>In the present paper we aimed to characterize epigenetic aspects and analyze <jats:italic>TP53<\/jats:italic> transcription in the 21\u2009T series, composed of breast cell lines: non\u2010cancerous H16N2; Atypical Ductal Hyperplasia 21PT; Ductal Carcinoma in situ 21NT and Invasive Metastatic Carcinoma 21MT1. We detected a global genomic hypomethylation in 21NT and 21MT1. The histone modification markers analysis showed an important global decrease of the active chromatin mark H4Ac in 21MT1 relative to the other cell lines while the repressive mark H3K9Me3 were not significantly altered. The mRNA levels of DNA methylation and histone modification key enzymes are consistent with the observed genomic hypomethylation and histone hypoacetylation. The expression of DNMT3A\/B increased at the initial stages of oncogenesis and the expression of DNMT1 and HAT1 decreased at the advanced stages of breast cancer. Using a confocal immunofluorescent assay, we observed that H4Ac was mostly located at the periphery and the repressive mark H3K9Me3, at the center of 21NT and 21MT1 cells nuclei. <jats:italic>TP53<\/jats:italic> P1 promoter was found to be in an open chromatin state, with a relatively high enrichment of H4Ac and similar <jats:italic>TP53<\/jats:italic> transcription levels in all 21\u2009T cell lines. In conclusion, we observed epigenetic alterations (global genome hypomethylation, global hypoacetylation and accumulation of pericentric heterochromatin) in metastatic breast cancer cells of the 21\u2009T series. These alterations may act at later stages of breast cancer progression and may not affect <jats:italic>TP53<\/jats:italic> transcription at the P1 promoter. J. Cell. Biochem. 116: 533\u2013541, 2015. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.25003","type":"journal-article","created":{"date-parts":[[2014,10,30]],"date-time":"2014-10-30T20:47:18Z","timestamp":1414702038000},"page":"533-541","source":"Crossref","is-referenced-by-count":10,"title":["Epigenetic Modifications, Chromatin Distribution and <i>TP53<\/i> Transcription in a Model of Breast Cancer Progression"],"prefix":"10.1002","volume":"116","author":[{"suffix":"Jr","given":"Gilson C.","family":"Santos","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica, Instituto de Biologia Roberto Alcantara Gomes Universidade do Estado do Rio de Janeiro Rio de Janeiro 20550\u2010013 Brazil"},{"name":"Universit\u00e9 Paris\u2010Sud 11 CNRS UMR 8126 \u00abSignalisation, Noyaux et Innovations en Canc\u00e9rologie\u00bb Institut de Canc\u00e9rologie Gustave\u2010Roussy Universit\u00e9 Paris\u2010Sud 11 F\u201094805 Villejuif Cedex France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana P. 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