Previous Article | Next Article ![]()
Molecular and Cellular Biology, July 2001, p. 4110-4118, Vol. 21, No. 13
Department of Oncological Sciences, Huntsman
Cancer Institute, University of Utah, Salt Lake City, Utah 84112-5550
Received 26 February 2001/Accepted 10 April 2001
The mSin3A-histone deacetylase corepressor is a multiprotein
complex that is recruited by DNA binding transcriptional repressors. Sin3 has four paired amphipathic alpha helices (PAH1 to -4) that are
protein-protein interaction motifs and is the scaffold upon which the
complex assembles. We identified a novel mSin3A-interacting protein
that has two plant homeodomain (PHD) zinc fingers we term Pf1, for PHD
factor one. Pf1 associates with mSin3A in vivo and recruits the mSin3A
complex to repress transcription when fused to the DNA binding domain
of Gal4. Pf1 interacts with Sin3 through two independent Sin3
interaction domains (SIDs), Pf1SID1 and Pf1SID2. Pf1SID1 binds PAH2,
while Pf1SID2 binds PAH1. Pf1SID1 has sequence and structural
similarity to the well-characterized 13-amino-acid SID of the Mad
bHLHZip repressor. Pf1SID2 does not have sequence similarity with
either Mad SID or Pf1SID1 and therefore represents a novel Sin3 binding
domain. Mutations in a minimal fragment of Pf1 that encompasses Pf1SID1
inhibited mSin3A binding yet only slightly impaired repression when
targeted to DNA, implying that Pf1 might interact with other
corepressors. We show that Pf1 interacts with a mammalian homolog of
the Drosophila Groucho corepressor, transducin-like
enhancer (TLE). Pf1 binds TLE in an mSin3A-independent manner and
recruits functional TLE complexes to repress transcription. These
findings suggest that Pf1 may serve to bridge two global transcription
networks, mSin3A and TLE.
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.13.4110-4118.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Pf1, a Novel PHD Zinc Finger Protein That Links the
TLE Corepressor to the mSin3A-Histone Deacetylase Complex
*
Corresponding author. Mailing address: Huntsman Cancer
Institute, University of Utah, 2000 Circle of Hope, Room 4365, Salt Lake City, UT 84112-5550. Phone: (801) 581-5597. Fax: (801) 585-1980. E-mail: don.ayer{at}hci.utah.edu.
This article has been cited by other articles:
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|