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PMID: 8265582 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Identification of human DNA topoisomerase I as a cofactor for activator-dependent transcription by RNA polymerase II.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 24 ·1993-12-15 ·Pages 11508-12

Kretzschmar M, Meisterernst M, Roeder RG

Abstract

The transcriptional activation of eukaryotic class II genes by sequence-specific regulatory proteins requires cofactors in addition to the general transcription factors. One cofactor (termed PC3) was purified from HeLa cells and identified by sequence analysis and functional assays as human DNA topoisomerase I (EC5.99.1.2). Under identical conditions PC3 mediates both a net activation of transcription by the acidic activator GAL4-AH and repression of basal transcription, thereby leading to a large induction of transcription by the activator. PC3-mediated activation of transcription is dependent on the presence of both the GAL4-AH activation domain and the TATA-binding protein (TBP)-associated-factors (TAFs) in natural transcription factor TFIID, while repression of basal transcription is observed with either TFIID or the derived TBP alone. These results suggest novel functions, apparently through distinct mechanisms, for human DNA topoisomerase I in the regulation of transcription initiation by RNA polymerase II.

MeSH Terms
Amino Acid Sequence Cell Nucleus/enzymology Chromatography, Ion Exchange DNA Topoisomerases, Type I/isolation & purification,metabolism DNA-Binding Proteins/metabolism Electrophoresis, Polyacrylamide Gel Gene Expression Regulation, Neoplastic HeLa Cells Humans Molecular Sequence Data Molecular Weight RNA Polymerase II/metabolism Recombinant Proteins/metabolism Sequence Homology, Amino Acid TATA-Box Binding Protein Transcription Factors/metabolism Transcription Factors, TFIII Transcription, Genetic
Chemicals
DNA-Binding Proteins Recombinant Proteins TATA-Box Binding Protein Transcription Factors Transcription Factors, TFIII transcription factor TFIIID RNA Polymerase II DNA Topoisomerases, Type I
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kretzschmar M
Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, NY 10021.
Meisterernst M
Roeder R G
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.24.11508
Published
1993-12-15
Pages
11508-12
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC48013
Subset
IM
Grants
NIAID NIH HHS · AI27397 · United States
NCI NIH HHS · CA42567 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.24.11508 PMC Full Text View journal details
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