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| ID:
536235.0,
MPI für molekulare Genetik / Independent Junior Research Groups (Otto-Warburg-Laboratory) |
| The KRAB-containing zinc-finger transcriptional regulator ZBRK1 activates SCA2 gene transcription through direct interaction with its gene product ataxin-2. |
| Authors: | Hallen, Linda; Klein, Holger; Stoschek, Carola; Wehrmeyer, Silke; Nonhoff, Ute; Ralser, Markus; Wilde, Jeannine; Röhr, Christina; Schweiger, Michal R.; Zatloukal, Kurt; Vingron, Martin; Lehrach, Hans; Konthur, Zoltán; Krobitsch, Sylvia | | Language: | English | | Research Context: | This work was supported by the Max Planck Society, the Ataxia UK Foundation (to Z.K. and S.K.), the German Federal Ministry for Education and Research, BMBF (NGFNII, 01GR0427 to Z.K., 01GS08111 to M.R.S.), the International Research Training Group-Genomics and Systems Biology of Molecular Networks (to H.K.). | | Date of Publication (YYYY-MM-DD): | 2010-10-06 | | Title of Journal: | Human Molecular Genetics. | | Journal Abbrev.: | Hum. Mol. Genet. | | Volume: | 20 | | Issue / Number: | 1 | | Start Page: | 104 | | End Page: | 114 | | Copyright: | © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com | | 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 an 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 tumors 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: | Email: krobitsc@molgen.mpg.de | | External Publication Status: | published | | Document Type: | Article | | Version Comment: | Automatic journal name synchronization |
| Communicated by: | OWL-Group | | Affiliations: | MPI für molekulare Genetik
| | External Affiliations: | 1.Department of Biology, Chemistry and Pharmacy, Free University Berlin, Takustrasse 3, 14195 Berlin, Germany;
2.Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria.
| | Identifiers: | URL:http://hmg.oxfordjournals.org/content/20/1/104.ful...
ISSN:0964-6906
DOI:10.1093/hmg/ddq436 |
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