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

J. S. Zhang, M. C. Moncrieffe, J. Kaczynski, V. Ellenrieder, F. G. Prendergast, R. Urrutia

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Sp1-like proteins are defined by three highly homologous C2H2 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 β-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 (α-HRM) located within the repression domain (R1) of TIEG2. This α-HRM specifically associates with the second paired amphipathic helix (PAH2) domain of mSin3A. Mutations in the TIEG2 α-HRM domain that disrupt its helical structure abolish its ability to both bind mSin3A and repress transcription. Interestingly, the α-HRM is conserved in both the TIEG (TIEG1 and TIEG2) and BTEB (BTEB1, BTEB3, and BTEB4) subfamilies of Sp1-like proteins. The α-HRM from these proteins also mediates direct interaction with mSin3A and represses transcription. Surprisingly, we found that the α-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 α-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.

Original languageEnglish (US)
Pages (from-to)5041-5049
Number of pages9
JournalMolecular and Cellular Biology
Volume21
Issue number15
DOIs
StatePublished - 2001

Fingerprint

Co-Repressor Proteins
Proteins
Histone Deacetylases
GC Rich Sequence
Essential Genes
Zinc Fingers
Transforming Growth Factors
Homeostasis
Mutation

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

A conserved α-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A. / Zhang, J. S.; Moncrieffe, M. C.; Kaczynski, J.; Ellenrieder, V.; Prendergast, F. G.; Urrutia, R.

In: Molecular and Cellular Biology, Vol. 21, No. 15, 2001, p. 5041-5049.

Research output: Contribution to journalArticle

Zhang, J. S. ; Moncrieffe, M. C. ; Kaczynski, J. ; Ellenrieder, V. ; Prendergast, F. G. ; Urrutia, R. / A conserved α-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A. In: Molecular and Cellular Biology. 2001 ; Vol. 21, No. 15. pp. 5041-5049.
@article{e600d410c5f54c918855d9ba0bd066d2,
title = "A conserved α-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A",
abstract = "Sp1-like proteins are defined by three highly homologous C2H2 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 β-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 (α-HRM) located within the repression domain (R1) of TIEG2. This α-HRM specifically associates with the second paired amphipathic helix (PAH2) domain of mSin3A. Mutations in the TIEG2 α-HRM domain that disrupt its helical structure abolish its ability to both bind mSin3A and repress transcription. Interestingly, the α-HRM is conserved in both the TIEG (TIEG1 and TIEG2) and BTEB (BTEB1, BTEB3, and BTEB4) subfamilies of Sp1-like proteins. The α-HRM from these proteins also mediates direct interaction with mSin3A and represses transcription. Surprisingly, we found that the α-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 α-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.",
author = "Zhang, {J. S.} and Moncrieffe, {M. C.} and J. Kaczynski and V. Ellenrieder and Prendergast, {F. G.} and R. Urrutia",
year = "2001",
doi = "10.1128/MCB.21.15.5041-5049.2001",
language = "English (US)",
volume = "21",
pages = "5041--5049",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "15",

}

TY - JOUR

T1 - A conserved α-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A

AU - Zhang, J. S.

AU - Moncrieffe, M. C.

AU - Kaczynski, J.

AU - Ellenrieder, V.

AU - Prendergast, F. G.

AU - Urrutia, R.

PY - 2001

Y1 - 2001

N2 - Sp1-like proteins are defined by three highly homologous C2H2 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 β-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 (α-HRM) located within the repression domain (R1) of TIEG2. This α-HRM specifically associates with the second paired amphipathic helix (PAH2) domain of mSin3A. Mutations in the TIEG2 α-HRM domain that disrupt its helical structure abolish its ability to both bind mSin3A and repress transcription. Interestingly, the α-HRM is conserved in both the TIEG (TIEG1 and TIEG2) and BTEB (BTEB1, BTEB3, and BTEB4) subfamilies of Sp1-like proteins. The α-HRM from these proteins also mediates direct interaction with mSin3A and represses transcription. Surprisingly, we found that the α-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 α-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.

AB - Sp1-like proteins are defined by three highly homologous C2H2 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 β-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 (α-HRM) located within the repression domain (R1) of TIEG2. This α-HRM specifically associates with the second paired amphipathic helix (PAH2) domain of mSin3A. Mutations in the TIEG2 α-HRM domain that disrupt its helical structure abolish its ability to both bind mSin3A and repress transcription. Interestingly, the α-HRM is conserved in both the TIEG (TIEG1 and TIEG2) and BTEB (BTEB1, BTEB3, and BTEB4) subfamilies of Sp1-like proteins. The α-HRM from these proteins also mediates direct interaction with mSin3A and represses transcription. Surprisingly, we found that the α-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 α-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.

UR - http://www.scopus.com/inward/record.url?scp=0034954161&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034954161&partnerID=8YFLogxK

U2 - 10.1128/MCB.21.15.5041-5049.2001

DO - 10.1128/MCB.21.15.5041-5049.2001

M3 - Article

C2 - 11438660

AN - SCOPUS:0034954161

VL - 21

SP - 5041

EP - 5049

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 15

ER -