PMID- 24948597 OWN - NLM STAT- MEDLINE DCOM- 20150102 LR - 20220409 IS - 1530-6860 (Electronic) IS - 0892-6638 (Print) IS - 0892-6638 (Linking) VI - 28 IP - 10 DP - 2014 Oct TI - Overexpression of histone deacetylases in cancer cells is controlled by interplay of transcription factors and epigenetic modulators. PG - 4265-79 LID - 10.1096/fj.14-250654 [doi] AB - 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. CI - (c) FASEB. FAU - Yang, Hui AU - Yang H AD - Department of Anatomy and Cell Biology and. FAU - Salz, Tal AU - Salz T AD - Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Zajac-Kaye, Maria AU - Zajac-Kaye M AD - Department of Anatomy and Cell Biology and. FAU - Liao, Daiqing AU - Liao D AD - Department of Anatomy and Cell Biology and. FAU - Huang, Suming AU - Huang S AD - Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida, USA qiuy@ufl.edu sumingh@ufl.edu. FAU - Qiu, Yi AU - Qiu Y AD - Department of Anatomy and Cell Biology and qiuy@ufl.edu sumingh@ufl.edu. LA - eng GR - R01-HL-090589/HL/NHLBI NIH HHS/United States GR - R01 HL095674/HL/NHLBI NIH HHS/United States GR - R01-HL-095674/HL/NHLBI NIH HHS/United States GR - R01-HL-091929/HL/NHLBI NIH HHS/United States GR - R01 HL091929/HL/NHLBI NIH HHS/United States GR - R01 HL090589/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140619 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) RN - EC 2.1.1.43 (Setd1A protein, human) RN - EC 2.3.1.48 (p300-CBP Transcription Factors) RN - EC 3.5.1.98 (HDAC1 protein, human) RN - EC 3.5.1.98 (HDAC2 protein, human) RN - EC 3.5.1.98 (Histone Deacetylase 1) RN - EC 3.5.1.98 (Histone Deacetylase 2) SB - IM MH - Colonic Neoplasms/*metabolism MH - *Epigenesis, Genetic MH - *Gene Expression Regulation, Neoplastic MH - HCT116 Cells MH - HT29 Cells MH - Histone Deacetylase 1/genetics/*metabolism MH - Histone Deacetylase 2/genetics/*metabolism MH - Histone-Lysine N-Methyltransferase/genetics/metabolism MH - Humans MH - Promoter Regions, Genetic MH - p300-CBP Transcription Factors/genetics/metabolism PMC - PMC4202103 OTO - NOTNLM OT - SET1 OT - Sp1 OT - Sp3 OT - p300 EDAT- 2014/06/21 06:00 MHDA- 2015/01/03 06:00 PMCR- 2015/10/01 CRDT- 2014/06/21 06:00 PHST- 2014/06/21 06:00 [entrez] PHST- 2014/06/21 06:00 [pubmed] PHST- 2015/01/03 06:00 [medline] PHST- 2015/10/01 00:00 [pmc-release] AID - fj.14-250654 [pii] AID - 14-250654 [pii] AID - 10.1096/fj.14-250654 [doi] PST - ppublish SO - FASEB J. 2014 Oct;28(10):4265-79. doi: 10.1096/fj.14-250654. Epub 2014 Jun 19.