Hepatocyte nuclear factor-3 homologue 1 (HFH-1) represses transcription of smooth muscle-specific genes

April M. Hoggatt, Alison M. Kriegel, Aiping F. Smith, B. Herring

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Results show that smooth muscle-specific promoters represent novel downstream targets of the winged helix factor hepatocyte nuclear factor-3 homologue 1 (HFH-1). HFH-1 strongly represses telokin promoter activity when overexpressed in A10 vascular smooth muscle cells. HFH-1 was also found to repress transcription of several other smooth muscle-specific promoters, including the SM22α promoter. HFH-1 inhibits telokin promoter activity, by binding to a forkhead consensus site located within an AT-rich region of the telokin promoter. The DNA-binding domain alone was sufficient to mediate inhibition, suggesting that binding of HFH-1 blocks the binding of other positive-acting factors, HFH-1 does not disrupt serum response factor binding to an adjacent CArG box within the telokin promoter, implying that HFH-1 must compete with other unidentified trans-activators to mediate repression. The localization of HFH-I mRNA to the epithelial cell layer of mouse bladder and stomach implicates HFH-1 in repressing telokin expression in epithelial cells. This suggests that cell-specific expression of telokin is likely mediated by both positive-acting factors in smooth muscle cells and negative-acting factors in nonmuscle cell types. We propose a model in which the smooth muscle specificity of the telokin promoter is regulated by interactions between positive- and negative-acting members of the hepatocyte nuclear factor-3/forkhead family of transcription factors.

Original languageEnglish
Pages (from-to)31162-31170
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number40
StatePublished - Oct 6 2000

Fingerprint

Hepatocyte Nuclear Factors
Transcription
Smooth Muscle
Muscle
Genes
Smooth Muscle Myocytes
Epithelial Cells
Cells
AT Rich Sequence
Serum Response Factor
Forkhead Transcription Factors
Trans-Activators
antineoplaston A10
telokin
Vascular Smooth Muscle
Stomach
Urinary Bladder
Transcription Factors

ASJC Scopus subject areas

  • Biochemistry

Cite this

Hoggatt, A. M., Kriegel, A. M., Smith, A. F., & Herring, B. (2000). Hepatocyte nuclear factor-3 homologue 1 (HFH-1) represses transcription of smooth muscle-specific genes. Journal of Biological Chemistry, 275(40), 31162-31170.

Hepatocyte nuclear factor-3 homologue 1 (HFH-1) represses transcription of smooth muscle-specific genes. / Hoggatt, April M.; Kriegel, Alison M.; Smith, Aiping F.; Herring, B.

In: Journal of Biological Chemistry, Vol. 275, No. 40, 06.10.2000, p. 31162-31170.

Research output: Contribution to journalArticle

Hoggatt, AM, Kriegel, AM, Smith, AF & Herring, B 2000, 'Hepatocyte nuclear factor-3 homologue 1 (HFH-1) represses transcription of smooth muscle-specific genes', Journal of Biological Chemistry, vol. 275, no. 40, pp. 31162-31170.
Hoggatt, April M. ; Kriegel, Alison M. ; Smith, Aiping F. ; Herring, B. / Hepatocyte nuclear factor-3 homologue 1 (HFH-1) represses transcription of smooth muscle-specific genes. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 40. pp. 31162-31170.
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