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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents



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ID: 555070.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
The KRAB-containing zinc-finger transcriptional regulator ZBRK1 activates SCA2 gene transcription through direct interaction with its gene product, ataxin-2
Authors:Hallen, L.; Klein, H.; Stoschek, C.; Wehrmeyer, S.; Nonhoff, U.; Ralser, M.; Wilde, J.; Rohr, C.; Schweiger, M. R.; Zatloukal, K.; Vingron, M.; Lehrach, H.; Konthur, Z.; Krobitsch, S.
Language:English
Date of Publication (YYYY-MM-DD):2011-01-20
Title of Journal:Human Molecular Genetics
Journal Abbrev.:Hum Mol Genet
Volume:20
Start Page:104
End Page:114
Copyright:© 2011Oxford University Press
Review Status:not specified
Audience:Experts Only
Abstract / Description:Gene transcription is controlled by transcriptional regulators acting with specific co-regulators to allow gene activation and repression. Here, we report the identification of the KRAB-containing zinc-finger transcriptional regulator, ZBRK1, as interaction partner of the SCA2 gene product ataxin-2. Furthermore, we discovered that an elevated ZBRK1 level resulted in increased ataxin-2 levels, whereas interference on transcriptional and protein levels of ZBRK1 yielded reduced ataxin-2 levels, suggesting that a complex comprising ZBRK1 and ataxin-2 regulates SCA2 gene transcription. A bioinformatic analysis utilizing the known ZBRK1 consensus DNA binding motif revealed ZBRK1 binding sites in the SCA2 promoter. These predicted sites were experimentally validated by chromatin-immunoprecipitation experiments along with luciferase-based promoter analyses corroborating that SCA2 gene transcription is controlled by a ZBRK1/ataxin-2 complex. Finally, we demonstrate that SCA2 gene transcription is significantly reduced in colon tumours possessing low ZBRK1 transcripts. Thus, our results provide first evidence that ataxin-2 acts as a co-regulator of ZBRK1 activating its own transcription, thereby representing the first identified ZBRK1 co-activator.
Comment of the Author/Creator:E-mail: krobitsc@molgen.mpg.de
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Department of Biology, Chemistry and Pharmacy, Free University Berlin, Takustrasse 3, 14195 Berlin, Germany
Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria
Identifiers:ISSN:1460-2083 (Electronic) [ID No:1]
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