Publikationsserver der RWTH Aachen University
Regulation des DNA-Polymerase-[alpha]-Gens durch den Transkriptionsfaktor YB-1
Abstract
dc:descriptionY-box protein-1 involvement in cyclin A and B1 gene regulation has recently been demonstrated (Jurchott, K., Bergmann S., Stein U., Walther W., Janz M., Manni I., Piaggio G., Fietze E., Dietel M., and Royer H.D. (2003) J. Biol. Chem. 278, 27988-96). A more generalised role of this protein for cell-replication is hypothesised as numerous regulatory sequences of cell-cycle related genes contain putative binding sites. In the present study the DNA polymerase Alpha (DPA) gene is identified as another YB-1 responsive gene with a Y-box and 3‘ inverted repeat sequence, designated DPA RE-1, in the serum-responsive promoter region. Overexpressed YB-1 concentration-dependently trans-activated DPA gene expression in reporter assays. Southwestern blotting and DNA binding analyses revealed binding of distinct endogenous proteins to the RE-1 with molecular sizes of 26, 32 and 52 kDa. Among these, YB-1 binding was confirmed using recombinant as well as endogenous proteins, with preferential single-stranded DNA binding. Early serum growth response in mesangial cells was accompanied by a nuclear YB-1 shift and nucleocomplex formation at the RE-1. Fine mapping of the DPA RE-1 sequence unravelled a dependency on co-factors for trans-regulation with gene activation in the context of a heterologous SV40 promoter, however suppression in the context of the abbreviated homologous promoter sequence. These results link YB-1 to serum-responsiveness of DPA gene expression and provide insight into the required sequence and protein binding context.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2005
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Yilmaz, Emek
- Contributors dc:contributor
-
- Mertens, Peter René
Subjects
dc:subject × 4Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- ger
Identifiers
dc:identifier.*- OAI identifier oai:identifier
- oai:publications.rwth-aachen.de:59874