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Albert, T.K. ; Grote, K.* ; Boeing, S. ; Stelzer, G. ; Schepers, A. ; Meisterernst, M.

Global distribution of negative cofactor 2 subunit-alpha on human promoters.

Proc. Natl. Acad. Sci. U.S.A. 104, 10000-10005 (2007)
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Negative cofactor 2 (NC2) forms a stable complex with TATA-binding protein (TBP) on promoters in vitro. Its association with TBP prevents the binding of TFIIB and leads to inhibition of preinitiation complex formation. Here, we investigate the association of NC2 subunit-alpha with human RNA polymerase II promoter regions by using gene-specific ChIP and genome-wide promoter ChIPchip analyses. We find NC2alpha associated with a large number of human promoters, where it peaks close to the core regions. NC2 occupancy in vivo positively correlates with mRNA levels, which perhaps reflects its capacity to stabilize TBP on promoter regions. In single gene analyses, we confirm core promoter binding and in addition map the NC2 complex to enhancer proximal regions. High-occupancy histone genes display a stable NC2/TFIIB ratio during the cell cycle, which otherwise varies markedly from one gene to another. The latter is at least in part explained by an observed negative correlation of NC2 occupancy with the presence of the TFIIB recognition element in core promoter regions. Our data establish the genome-wide basis for general and gene-specific functions of NC2 in mammalian cells.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords genome-wide; occupancy; RNA-POLYMERASE-II; TATA-BINDING PROTEIN; TRANSCRIPTION IN-VIVO; GENOME-WIDE LOCATION; SACCHAROMYCES-CEREVISIAE; NEGATIVE COFACTOR-2; GENE-TRANSCRIPTION; CRYSTAL-STRUCTURE; ACTIVE PROMOTERS; NC2
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 104, Issue: 24, Pages: 10000-10005 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)
Research Unit Gene Vector (AGV)