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 Previous Article

Molecular and Cellular Biology, March 2008, p. 2102-2112, Vol. 28, No. 6
0270-7306/08/$08.00+0     doi:10.1128/MCB.01943-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

C/EBPβ Induces Chromatin Opening at a Cell-Type-Specific Enhancer{triangledown}

Annette Plachetka,1 Olesya Chayka,1,{dagger} Carola Wilczek,1 Svitlana Melnik,2,{ddagger} Constanze Bonifer,2 and Karl-Heinz Klempnauer1*

Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, D-48149 Münster, Germany,1 Division of Experimental Haematology, LIMM, University of Leeds, St. James's University Hospital, Leeds LS9 7TF, United Kingdom2

Received 29 October 2007/ Returned for modification 16 December 2007/ Accepted 1 January 2008

We have used the chicken mim-1 gene as a model to study the mechanisms by which transcription factors gain initial access to their target sites in compacted chromatin. The expression of mim-1 is restricted to the myelomonocytic lineage of the hematopoietic system where it is regulated synergistically by the Myb and CCAAT/enhancer binding protein (C/EBP) factors. Myb and C/EBPβ cooperate at two distinct cis elements of mim-1, the promoter and a cell-type-specific enhancer, both of which are associated with DNase I hypersensitive sites in myelomonocytic cells but not in mim-1-nonexpressing cells. Previous work has shown that ectopic expression of Myb and C/EBPβ activates the endogenous mim-1 gene in a nonhematopoietic cell type (fibroblasts), where the gene is normally completely silent. Here, we investigated the molecular details of this finding and show that the activation of mim-1 occurs by two independent mechanisms. In the absence of Myb, C/EBPβ triggers the initial steps of chromatin opening at the mim-1 enhancer without inducing transcription of the gene. mim-1 transcription occurs only in the presence of Myb and is associated with chromatin opening at the promoter. Our work identifies a novel function for C/EBPβ in the initial steps of a localized chromatin opening at a specific, physiologically relevant target region.

* Corresponding author. Mailing address: Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, D-48149 Münster, Germany. Phone: 49-251-8333203. Fax: 49-251-8333206. E-mail: klempna{at}uni-muenster.de

{triangledown} Published ahead of print on 14 January 2008.

{dagger} Present address: Institute of Child Health, Molecular Haematology and Cancer Biology Unit, 30 Guilford Street, London WC1N 1EH, United Kingdom.

{ddagger} Present address: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom.

Molecular and Cellular Biology, March 2008, p. 2102-2112, Vol. 28, No. 6
0270-7306/08/$08.00+0     doi:10.1128/MCB.01943-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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