Overexpression of histone deacetylases in cancer cells is controlled by interplay of transcription factors and epigenetic modulators

Hui Yang, Tal Salz, Maria Zajac-Kaye, Daiqing Liao, Suming Huang, Yi Qiu

Research output: Contribution to journalArticle

19 Citations (Scopus)

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

Original languageEnglish (US)
Pages (from-to)4265-4279
Number of pages15
JournalFASEB Journal
Volume28
Issue number10
DOIs
StatePublished - Oct 1 2014

Fingerprint

Histone Deacetylases
Epigenomics
Modulators
Transcription Factors
Cells
Histones
Colonic Neoplasms
Sp3 Transcription Factor
Sp1 Transcription Factor
Histone Acetyltransferases
Acetylation
Neoplasms
Cell proliferation
Methyltransferases
Crosstalk
Cell Survival
Chemical activation
Cell Proliferation
Cell Line
Proteins

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Yang, Hui ; Salz, Tal ; Zajac-Kaye, Maria ; Liao, Daiqing ; Huang, Suming ; Qiu, Yi. / Overexpression of histone deacetylases in cancer cells is controlled by interplay of transcription factors and epigenetic modulators. In: FASEB Journal. 2014 ; Vol. 28, No. 10. pp. 4265-4279.
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Overexpression of histone deacetylases in cancer cells is controlled by interplay of transcription factors and epigenetic modulators. / Yang, Hui; Salz, Tal; Zajac-Kaye, Maria; Liao, Daiqing; Huang, Suming; Qiu, Yi.

In: FASEB Journal, Vol. 28, No. 10, 01.10.2014, p. 4265-4279.

Research output: Contribution to journalArticle

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