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  The KRAB-containing zinc-finger transcriptional regulator ZBRK1 activates SCA2 gene transcription through direct interaction with its gene product, ataxin-2

Hallen, L., Klein, H., Stoschek, C., Wehrmeyer, S., Nonhoff, U., Ralser, M., et al. (2011). The KRAB-containing zinc-finger transcriptional regulator ZBRK1 activates SCA2 gene transcription through direct interaction with its gene product, ataxin-2. Human Molecular Genetics, 20, 104-114.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-77CF-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-77D0-4
Genre: Journal Article
Alternative Title : Hum Mol Genet

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 Creators:
Hallen, L.1, Author              
Klein, H.2, Author
Stoschek, C.3, Author              
Wehrmeyer, S.4, Author              
Nonhoff, U.1, Author              
Ralser, M.1, Author              
Wilde, J.1, Author              
Rohr, C.5, Author              
Schweiger, M. R.5, Author              
Zatloukal, K., Author
Vingron, M.6, Author              
Lehrach, H.1, Author              
Konthur, Z.3, Author              
Krobitsch, S.7, Author              
Affiliations:
1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
2Max Planck Society, ou_persistent13              
3In vitro Ligand Screening (Zoltán Konthur), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479653              
4Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433554              
5Cancer Genomics (Michal-Ruth Schweiger), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479649              
6Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              
7Neurodegenerative Disorders (Sylvia Krobitsch), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479661              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2011-01-20
 Publication Status: Published in print
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 Identifiers: eDoc: 555070
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Title: Human Molecular Genetics
  Alternative Title : Hum Mol Genet
Source Genre: Journal
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Pages: - Volume / Issue: 20 Sequence Number: - Start / End Page: 104 - 114 Identifier: ISSN: 1460-2083 (Electronic)