Acetylated Sp3 is a transcriptional activator

Sudhakar Ammanamanchi, James W. Freeman, Michael G. Brattain

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Sp3 transcription factor can either activate or repress target gene expression. However, the molecular event that controls this dual function is unclear. We previously reported (Ammanamanchi, S., and Brattain, M. G. (2001) J. Biol. Chem. 276, 3348-3352) that unmodified Sp3 acts as a transcriptional repressor of transforming growth factor-β receptors in MCF-7L breast cancer cells. We now report that histone deacetylase inhibitor trichostatin A (TSA) induces acetylation of Sp3, which acts as a transcriptional activator of transforming growth factor-β receptor type II (RII) in MCF-7L cells. Mutation analysis indicated the TSA response is mediated through a GC box located on the RII promoter, which was previously identified as an Sp1/Sp3-binding site that was critical for RII promoter activity. Ectopic Sp3 expression in Sp3-deficient MCF-7E breast cancer cells repressed RII promoter activity in the absence of TSA. However, in the TSA-treated MCF-7E cells ectopic Sp3 activated RII promoter. Histone acetyltransferase p300 was shown to acetylate Sp3. Sp3-mediated RII promoter activity was stimulated by wild type p300 but not the histone acetyltransferase domain-deleted mutant p300 in MCF-7L cells, suggesting the positive effect of p300 acetylase activity on Sp3. Consequently, the results presented in this manuscript demonstrate that acetylation acts as a switch that controls the repressor and activator role of Sp3.

Original languageEnglish (US)
Pages (from-to)35775-35780
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number37
DOIs
StatePublished - Sep 12 2003

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trichostatin A
Histone Acetyltransferases
Acetylation
Growth Factor Receptors
Transforming Growth Factors
Sp3 Transcription Factor
Cells
Acetylesterase
Histone Deacetylase Inhibitors
Breast Neoplasms
Gene expression
Binding Sites
Switches
Gene Expression
Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ammanamanchi, S., Freeman, J. W., & Brattain, M. G. (2003). Acetylated Sp3 is a transcriptional activator. Journal of Biological Chemistry, 278(37), 35775-35780. https://doi.org/10.1074/jbc.M305961200

Acetylated Sp3 is a transcriptional activator. / Ammanamanchi, Sudhakar; Freeman, James W.; Brattain, Michael G.

In: Journal of Biological Chemistry, Vol. 278, No. 37, 12.09.2003, p. 35775-35780.

Research output: Contribution to journalArticle

Ammanamanchi, S, Freeman, JW & Brattain, MG 2003, 'Acetylated Sp3 is a transcriptional activator', Journal of Biological Chemistry, vol. 278, no. 37, pp. 35775-35780. https://doi.org/10.1074/jbc.M305961200
Ammanamanchi S, Freeman JW, Brattain MG. Acetylated Sp3 is a transcriptional activator. Journal of Biological Chemistry. 2003 Sep 12;278(37):35775-35780. https://doi.org/10.1074/jbc.M305961200
Ammanamanchi, Sudhakar ; Freeman, James W. ; Brattain, Michael G. / Acetylated Sp3 is a transcriptional activator. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 37. pp. 35775-35780.
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