| ZEB1 and CtBP form a repressive complex at a distal promoter element of the BCL6 locus. | |
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MedLine Citation:
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PMID: 20175752 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BCL6 is essential for normal antibody responses and is highly expressed in germinal centre B-cells. Constitutive expression due to chromosomal translocations or mutations of cis-acting regulatory elements contributes to diffuse large B-cell lymphoma. BCL6 expression is therefore tightly regulated in a lineage- and developmental-stage-specific manner, and disruption of normal controls can contribute to lymphomagenesis. In order to discover potential cis-acting control regions we carried out DNase I-hypersensitive site mapping. Gel-shift assays and chromatin immunoprecipitation of the core region of a hypersensitive site 4.4 kb upstream of BCL6 transcription initiation (HSS-4.4) showed an E-box element-binding ZEB1 (zinc finger E-boxbinding homeobox 1) and the co-repressor CtBP (C-terminal binding protein). As compared with peripheral blood B-cells, ZEB1, a two-handed zinc finger transcriptional repressor, is expressed at relatively low levels in germinal centre cells, whereas BCL6 has the opposite pattern of expression. Transfection of ZEB1 cDNA caused a reduction in BCL6 expression and a mutated ZEB1, incapable of binding CtBP, lacked this effect. siRNA (small interfering RNA)-mediated knockdown of ZEB1 or CtBP produced an increase in BCL6 mRNA. We propose that HSS-4.4 is a distal promoter element binding a repressive complex consisting of ZEB1 and CtBP. CtBP is ubiquitously expressed and the results of the present study suggest that regulation of ZEB1 is required for control of BCL6 expression. |
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Authors:
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Vasiliki Papadopoulou; Antonio Postigo; Ester S?nchez-Till?; Andrew C G Porter; Simon D Wagner |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-14 |
Journal Detail:
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Title: The Biochemical journal Volume: 427 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-14 Completed Date: 2010-04-20 Revised Date: 2010-06-29 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 541-50 Citation Subset: IM |
Affiliation:
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Department of Haematology, Imperial College London, Hammersmith Hospital, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alcohol Oxidoreductases
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genetics,
metabolism* Base Sequence Cell Line Cell Line, Tumor Chromatin Immunoprecipitation DNA-Binding Proteins / genetics*, metabolism* Homeodomain Proteins / genetics, metabolism* Humans Molecular Sequence Data Promoter Regions, Genetic / genetics Protein Binding / genetics RNA, Small Interfering Reverse Transcriptase Polymerase Chain Reaction Sequence Homology, Amino Acid Transcription Factors / genetics, metabolism* Transcription Initiation Site |
| Chemical | |
Reg. No./Substance:
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0/BCL6 protein, human; 0/DNA-Binding Proteins; 0/Homeodomain Proteins; 0/RNA, Small Interfering; 0/Transcription Factors; 0/ZEB1 protein, human; EC 1.1.-/Alcohol Oxidoreductases; EC 1.1.1.-/C-terminal binding protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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