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PMID: 8670811 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A mechanism for repression of class II gene transcription through specific binding of NC2 to TBP-promoter complexes via heterodimeric histone fold domains.

The EMBO journal ·Vol. 15 ·No. 12 ·1996-06-17 ·Pages 3105-16

Goppelt A, Stelzer G, Lottspeich F, Meisterernst M

Abstract

Negative co-factor 2 (NC2) regulates transcription of the class II genes through binding to TFIID and inhibition of pre-initiation complex formation. We have isolated and cloned NC2, and investigated the molecular mechanism underlying repression of transcription. NC2 consists of two subunits, termed NC2alpha and NC2beta, the latter of which is identical to Dr1. The NC2 subunits dimerize and bind to TATA binding protein (TBP)-promoter complexes via histone fold domains of the H2A-H2B type. Repression of basal transcription requires the histone fold and carboxy-terminal domains of the NC2 subunits. Several mechanisms probably contribute to transcriptional repression. Binding of NC2 inhibits association of TFIIB with TBP-promoter complexes. NC2 binds directly to DNA, and binding of NC2 to TBP-promoter complexes affects the conformation of DNA, which could be one cause for the inhibition of TFIIB. In addition, multimerization of repressor-TBP complexes on DNA might inhibit the assembly of the pre-initiation complex. We suggest that binding of the repressor to TRP-promoter complexes establishes a mechanism that controls the rate of transcription by RNA polymerase II.

MeSH Terms
Amino Acid Sequence Base Sequence Casein Kinase II Cloning, Molecular DNA, Complementary DNA-Binding Proteins/metabolism HeLa Cells Histocompatibility Antigens Class II/genetics Histones/metabolism Humans Molecular Sequence Data Phosphoproteins/metabolism Promoter Regions, Genetic Protein Binding Protein Folding Protein Serine-Threonine Kinases/metabolism Sequence Homology, Amino Acid TATA Box TATA-Box Binding Protein Transcription Factors/metabolism Transcription, Genetic
Chemicals
DNA, Complementary DNA-Binding Proteins Histocompatibility Antigens Class II Histones Phosphoproteins TATA-Box Binding Protein Transcription Factors down-regulator of transcription 1 Casein Kinase II Protein Serine-Threonine Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Goppelt A
Laboratorium für Molekulare Biologie-Genzentrum der Ludwig-Maximilians-Universität München, Germany.
Stelzer G
Lottspeich F
Meisterernst M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-06-17
Pages
3105-16
Language
English
Region
England
NLM ID
8208664
PMCID
PMC450253
Subset
IM
Databases
GENBANK
X96506
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