HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations

Kurt A. Swanson, Paul S Knoepfler, Kai Huang, Richard S. Kang, Shaun M. Cowley, Carol D. Laherty, Robert N. Eisenman, Ishwar Radhakrishnan

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Recruitment of the histone deacetylase (HDAC)-associated Sin3 corepressor is an obligatory step in many eukaryotic gene silencing pathways. Here we show that HBP1, a cell cycle inhibitor and regulator of differentiation, represses transcription in a HDAC/Sin3-dependent manner by targeting the mammalian Sin3A (mSin3A) PAH2 domain. HBP1 is unrelated to the Mad1 repressor for which high-resolution structures in complex with PAH2 have been described. We show that like Mad1, the HBP1 transrepression domain binds through a helical structure to the hydrophobic cleft of mSin3A PAH2. Notably, the HBP1 helix binds PAH2 in a reversed orientation relative to Mad1 and, equally unexpectedly, this is correlated with a chain reversal of the minimal Sin3 interaction motifs. These results not only provide insights into how multiple, unrelated transcription factors recruit the same coregulator, but also have implications for how sequence similarity searches are conducted.

Original languageEnglish (US)
Pages (from-to)738-746
Number of pages9
JournalNature Structural and Molecular Biology
Volume11
Issue number8
DOIs
StatePublished - Aug 2004
Externally publishedYes

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Co-Repressor Proteins
Histone Deacetylases
Gene Silencing
Cell Cycle
Transcription Factors

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations. / Swanson, Kurt A.; Knoepfler, Paul S; Huang, Kai; Kang, Richard S.; Cowley, Shaun M.; Laherty, Carol D.; Eisenman, Robert N.; Radhakrishnan, Ishwar.

In: Nature Structural and Molecular Biology, Vol. 11, No. 8, 08.2004, p. 738-746.

Research output: Contribution to journalArticle

Swanson, KA, Knoepfler, PS, Huang, K, Kang, RS, Cowley, SM, Laherty, CD, Eisenman, RN & Radhakrishnan, I 2004, 'HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations', Nature Structural and Molecular Biology, vol. 11, no. 8, pp. 738-746. https://doi.org/10.1038/nsmb798
Swanson, Kurt A. ; Knoepfler, Paul S ; Huang, Kai ; Kang, Richard S. ; Cowley, Shaun M. ; Laherty, Carol D. ; Eisenman, Robert N. ; Radhakrishnan, Ishwar. / HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations. In: Nature Structural and Molecular Biology. 2004 ; Vol. 11, No. 8. pp. 738-746.
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