Title: Overexpression of histone deacetylases in cancer cells is controlled by interplay of transcription factors and epigenetic modulators
Abstract: The FASEB JournalVolume 28, Issue 10 p. 4265-4279 Research CommunicationFree to Read Overexpression of histone deacetylases in cancer cells is controlled by interplay of transcription factors and epigenetic modulators Hui Yang, Hui Yang Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, Florida, USASearch for more papers by this authorTal Salz, Tal Salz Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida, USASearch for more papers by this authorMaria Zajac-Kaye, Maria Zajac-Kaye Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, Florida, USASearch for more papers by this authorDaiqing Liao, Daiqing Liao Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, Florida, USASearch for more papers by this authorSuming Huang, Corresponding Author Suming Huang [email protected] Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida, USACorrespondence: 2033 Mowry Rd., Room 356, Gainesville, FL 32610, USA. E-mail: [email protected]; 2033 Mowry Rd., Room 355, Gainesville, FL 32610, USA. E-mail: [email protected] for more papers by this authorYi Qiu, Corresponding Author Yi Qiu [email protected] Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, Florida, USACorrespondence: 2033 Mowry Rd., Room 356, Gainesville, FL 32610, USA. E-mail: [email protected]; 2033 Mowry Rd., Room 355, Gainesville, FL 32610, USA. E-mail: [email protected] for more papers by this author Hui Yang, Hui Yang Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, Florida, USASearch for more papers by this authorTal Salz, Tal Salz Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida, USASearch for more papers by this authorMaria Zajac-Kaye, Maria Zajac-Kaye Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, Florida, USASearch for more papers by this authorDaiqing Liao, Daiqing Liao Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, Florida, USASearch for more papers by this authorSuming Huang, Corresponding Author Suming Huang [email protected] Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida, USACorrespondence: 2033 Mowry Rd., Room 356, Gainesville, FL 32610, USA. E-mail: [email protected]; 2033 Mowry Rd., Room 355, Gainesville, FL 32610, USA. E-mail: [email protected] for more papers by this authorYi Qiu, Corresponding Author Yi Qiu [email protected] Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, Florida, USACorrespondence: 2033 Mowry Rd., Room 356, Gainesville, FL 32610, USA. E-mail: [email protected]; 2033 Mowry Rd., Room 355, Gainesville, FL 32610, USA. E-mail: [email protected] for more papers by this author First published: 19 June 2014 https://doi.org/10.1096/fj.14-250654Citations: 1 This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Histone deacetylases (HDACs) that deacetylate histone and nonhistone proteins play crucial roles in a variety of cellular processes. The overexpression of HDACs is reported in many cancer types and is directly linked to accelerated cell proliferation and survival. However, little is known about how HDAC expression is regulated in cancer cells. In this study, we found that HDAC1 and HDAC2 promoters are regulated through collaborative binding of transcription factors Sp1/Sp3 and epigenetic modulators, including histone H3K4 methyltransferase SET1 and histone acetyltransferase p300, whose levels are also elevated in colon cancer cell lines and patient samples. Interestingly, Sp1 and Sp3 differentially regulate HDAC1 and HDAC2 promoter activity. In addition, Sp1/Sp3 recruits SET1 and p300 to the promoters. SET1 knockdown (KD) results in a loss of the H3K4 trimethylation mark at the promoters, as well as destabilizes p300 at the promoters. Conversely, p300 also influences SET1 recruitment and H3K4me3 level, indicating a crosstalk between p300 and SET1. Further, SET1 KD reduces Sp1 binding to the HDAC1 promoter through the increase of Sp1 acetylation. These results indicate that interactions among transcription factors and epigenetic modulators orchestrate the activation of HDAC1 and HDAC2 promoter activity in colon cancer cells.—Yang, H., Salz, T., Zajac-Kaye, M., Liao, D., Huang, S., and Qiu, Y., Overexpression of histone deacetylases in cancer cells is controlled by interplay of transcription factors and epigenetic modulators. FASEB J. 28, 4265–4279 (2014). www.fasebj.org Citing Literature Supporting Information Filename Description fsb2028010008-sup-0001.zipZip archive, 195.3 KB Supplementary material Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume28, Issue10October 2014Pages 4265-4279 RelatedInformation