A conserved alpha-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A.

Abstract:

:Sp1-like proteins are defined by three highly homologous C(2)H(2) zinc finger motifs that bind GC-rich sequences found in the promoters of a large number of genes essential for mammalian cell homeostasis. Here we report that TIEG2, a transforming growth factor beta-inducible Sp1-like protein with antiproliferative functions, represses transcription through recruitment of the mSin3A-histone deacetylase complex. The interaction of TIEG2 with mSin3A is mediated by an alpha-helical repression motif (alpha-HRM) located within the repression domain (R1) of TIEG2. This alpha-HRM specifically associates with the second paired amphipathic helix (PAH2) domain of mSin3A. Mutations in the TIEG2 alpha-HRM domain that disrupt its helical structure abolish its ability to both bind mSin3A and repress transcription. Interestingly, the alpha-HRM is conserved in both the TIEG (TIEG1 and TIEG2) and BTEB (BTEB1, BTEB3, and BTEB4) subfamilies of Sp1-like proteins. The alpha-HRM from these proteins also mediates direct interaction with mSin3A and represses transcription. Surprisingly, we found that the alpha-HRM of the Sp1-like proteins characterized here exhibits structural and functional resemblance to the Sin3A-interacting domain previously described for the basic helix-loop-helix protein Mad1. Thus, our study defines a mechanism of transcriptional repression via the interactions of the alpha-HRM with the Sin3-histone deacetylase complex that is utilized by at least five Sp1-like transcriptional factors. More importantly, we demonstrate that a helical repression motif which mediates Sin3 interaction is not an exclusive structural and functional characteristic of the Mad1 subfamily but rather has a wider functional impact on transcriptional repression than previously demonstrated.

journal_name

Mol Cell Biol

authors

Zhang JS,Moncrieffe MC,Kaczynski J,Ellenrieder V,Prendergast FG,Urrutia R

doi

10.1128/MCB.21.15.5041-5049.2001

subject

Has Abstract

pub_date

2001-08-01 00:00:00

pages

5041-9

issue

15

eissn

0270-7306

issn

1098-5549

journal_volume

21

pub_type

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