The transcriptional corepressor DSP1 inhibits activated transcription by disrupting TFIIA-TBP complex formation

Nikolai C. Kirov, Paul M. Lieberman, Christine Rushlow

Research output: Contribution to journalArticle

Abstract

Transcriptional repression of eukaryotic genes is essential for many cellular and developmental processes, yet the precise mechanisms of repression remain poorly understood. The Dorsal Switch Protein (DSP1) was identified in a genetic screen for activities which convert Dorsal into a transcriptional repressor. DSP1 shares structural homology with the HMG-1/2 family and inhibits activation by the rel transcription factors Dorsal and NF-κB in transfection studies. Here we investigate the mechanism of transcriptional repression by DSP1. We found that DSP1 protein can act as a potent transcriptional repressor for multiple activator families in vitro and in transfection studies. DSP1 bound directly to the TATA binding protein (TBP), and formed a stable ternary complex with TBP bound to DNA. DSP1 preferentially disrupted the DNA binding of TBP complexes containing TFIIA and displaced TFIIA from binding to TBP. Consistent with the inhibition of TPIIA-bound complexes, DSP1 was shown to inhibit activated but not basal transcription reactions in vitro. The ability of DSP1 to interact with TBP and to repress transcription was mapped to the carboxy-terminal domain which contains two HMG boxes. Our results support the model that DSP1 represses activated transcription by interfering with the binding of TFIIA, a general transcription factor implicated in activated transcription pathways.

Original languageEnglish (US)
Pages (from-to)7079-7087
Number of pages9
JournalEMBO Journal
Volume15
Issue number24
StatePublished - 1996

Fingerprint

Transcription Factor TFIIA
TATA-Box Binding Protein
Co-Repressor Proteins
Transcription
Transfection
HMGB2 Protein
General Transcription Factors
DNA
Essential Genes
Proteins
Transcription Factors
Genes
Chemical activation
Switches

Keywords

  • Activated transcription
  • Dorsal Switch Protein
  • Repression
  • TFIIA-TBP complex

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

The transcriptional corepressor DSP1 inhibits activated transcription by disrupting TFIIA-TBP complex formation. / Kirov, Nikolai C.; Lieberman, Paul M.; Rushlow, Christine.

In: EMBO Journal, Vol. 15, No. 24, 1996, p. 7079-7087.

Research output: Contribution to journalArticle

@article{234312d5446c4ed380f82e1b310b9526,
title = "The transcriptional corepressor DSP1 inhibits activated transcription by disrupting TFIIA-TBP complex formation",
abstract = "Transcriptional repression of eukaryotic genes is essential for many cellular and developmental processes, yet the precise mechanisms of repression remain poorly understood. The Dorsal Switch Protein (DSP1) was identified in a genetic screen for activities which convert Dorsal into a transcriptional repressor. DSP1 shares structural homology with the HMG-1/2 family and inhibits activation by the rel transcription factors Dorsal and NF-κB in transfection studies. Here we investigate the mechanism of transcriptional repression by DSP1. We found that DSP1 protein can act as a potent transcriptional repressor for multiple activator families in vitro and in transfection studies. DSP1 bound directly to the TATA binding protein (TBP), and formed a stable ternary complex with TBP bound to DNA. DSP1 preferentially disrupted the DNA binding of TBP complexes containing TFIIA and displaced TFIIA from binding to TBP. Consistent with the inhibition of TPIIA-bound complexes, DSP1 was shown to inhibit activated but not basal transcription reactions in vitro. The ability of DSP1 to interact with TBP and to repress transcription was mapped to the carboxy-terminal domain which contains two HMG boxes. Our results support the model that DSP1 represses activated transcription by interfering with the binding of TFIIA, a general transcription factor implicated in activated transcription pathways.",
keywords = "Activated transcription, Dorsal Switch Protein, Repression, TFIIA-TBP complex",
author = "Kirov, {Nikolai C.} and Lieberman, {Paul M.} and Christine Rushlow",
year = "1996",
language = "English (US)",
volume = "15",
pages = "7079--7087",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "24",

}

TY - JOUR

T1 - The transcriptional corepressor DSP1 inhibits activated transcription by disrupting TFIIA-TBP complex formation

AU - Kirov, Nikolai C.

AU - Lieberman, Paul M.

AU - Rushlow, Christine

PY - 1996

Y1 - 1996

N2 - Transcriptional repression of eukaryotic genes is essential for many cellular and developmental processes, yet the precise mechanisms of repression remain poorly understood. The Dorsal Switch Protein (DSP1) was identified in a genetic screen for activities which convert Dorsal into a transcriptional repressor. DSP1 shares structural homology with the HMG-1/2 family and inhibits activation by the rel transcription factors Dorsal and NF-κB in transfection studies. Here we investigate the mechanism of transcriptional repression by DSP1. We found that DSP1 protein can act as a potent transcriptional repressor for multiple activator families in vitro and in transfection studies. DSP1 bound directly to the TATA binding protein (TBP), and formed a stable ternary complex with TBP bound to DNA. DSP1 preferentially disrupted the DNA binding of TBP complexes containing TFIIA and displaced TFIIA from binding to TBP. Consistent with the inhibition of TPIIA-bound complexes, DSP1 was shown to inhibit activated but not basal transcription reactions in vitro. The ability of DSP1 to interact with TBP and to repress transcription was mapped to the carboxy-terminal domain which contains two HMG boxes. Our results support the model that DSP1 represses activated transcription by interfering with the binding of TFIIA, a general transcription factor implicated in activated transcription pathways.

AB - Transcriptional repression of eukaryotic genes is essential for many cellular and developmental processes, yet the precise mechanisms of repression remain poorly understood. The Dorsal Switch Protein (DSP1) was identified in a genetic screen for activities which convert Dorsal into a transcriptional repressor. DSP1 shares structural homology with the HMG-1/2 family and inhibits activation by the rel transcription factors Dorsal and NF-κB in transfection studies. Here we investigate the mechanism of transcriptional repression by DSP1. We found that DSP1 protein can act as a potent transcriptional repressor for multiple activator families in vitro and in transfection studies. DSP1 bound directly to the TATA binding protein (TBP), and formed a stable ternary complex with TBP bound to DNA. DSP1 preferentially disrupted the DNA binding of TBP complexes containing TFIIA and displaced TFIIA from binding to TBP. Consistent with the inhibition of TPIIA-bound complexes, DSP1 was shown to inhibit activated but not basal transcription reactions in vitro. The ability of DSP1 to interact with TBP and to repress transcription was mapped to the carboxy-terminal domain which contains two HMG boxes. Our results support the model that DSP1 represses activated transcription by interfering with the binding of TFIIA, a general transcription factor implicated in activated transcription pathways.

KW - Activated transcription

KW - Dorsal Switch Protein

KW - Repression

KW - TFIIA-TBP complex

UR - http://www.scopus.com/inward/record.url?scp=0030478374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030478374&partnerID=8YFLogxK

M3 - Article

VL - 15

SP - 7079

EP - 7087

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 24

ER -