Novel regulatory role for human Acf1 in transcriptional repression of vitamin D3 receptor-regulated genes

Amy K. Ewing, Michelle Attner, Debabrata Chakravarti*

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Hormones and vitamins play integral roles in modulating transcriptional activity of members of the nuclear hormone receptor (NR) superfamily. The nuclear receptor corepressor protein (N-CoR) is essential for the transcriptional repression by unliganded NRs. In an attempt to isolate novel components of the hormone signaling pathway, we used a yeast two-hybrid screen and identified human ATP-utilizing chromatin assembly and remodeling factor 1 (hAcf1) as an N-CoR interacting protein. A previously unrecognized function of hAcf1 in the repression of euchromatic genes in mammalian cells was found: hAcf1 plays key roles in the hormone responsiveness and in the transcriptional repression of specific class II NR-regulated genes. First, hormone treatment causes a significant release of hAcf1 from its target gene promoters. Second, hAcf1 is crucial for stabilizing the endogenous vitamin D receptor-N-CoR repression complex and N-CoR itself, in the vitamin D3-regulated IGF binding protein 3 and receptor activator of nuclear factor-κB ligand gene promoters, respectively. Third, RNA interference-mediated reduction of hAcf1 or vitamin D3 treatment differentially affects the histone modification profile and the histone occupancy in these genes. Together, these results establish that hAcf1 has a critical role in the transcriptional repression of specific NR-regulated genes and indicate that hAcf1 release and histone H3 and H4 eviction are novel mechanisms in hormone-induced gene activation.

Original languageEnglish (US)
Pages (from-to)1791-1806
Number of pages16
JournalMolecular Endocrinology
Volume21
Issue number8
DOIs
StatePublished - Aug 3 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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