C/EBP beta induces chromatin opening at a cell-type-specific enhancer

Research output: Contribution to journalArticle

Authors

  • A Plachetka
  • O Chayka
  • C Wilczek
  • S Melnik
  • KH Klempnauer

Colleges, School and Institutes

Abstract

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/EBP beta 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/EBP beta 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/EBP beta 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/EBP beta in the initial steps of a localized chromatin opening at a specific, physiologically relevant target region.

Details

Original languageEnglish
Pages (from-to)2102-2112
Number of pages11
JournalMolecular and Cellular Biology
Volume28
Issue number6
Early online date14 Jan 2008
Publication statusPublished - 1 Mar 2008

Keywords

  • chromatin opening, C/EBP beta