C/EBPbeta induces chromatin opening at a cell-type-specific enhancer.

Mol Cell Biol 2008 Mar 14;28(6):2102-12. Epub 2008 Jan 14.

Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, D-48149 Münster, Germany.

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

Download full-text PDF

Source
http://dx.doi.org/10.1128/MCB.01943-07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268399PMC
March 2008
3 Reads

Publication Analysis

Top Keywords

chromatin opening
16
myb c/ebpbeta
12
cell-type-specific enhancer
8
mim-1 gene
8
initial steps
8
mim-1
7
c/ebpbeta
5
myb
5
chromatin
5
activates endogenous
4
type fibroblasts
4
cell type
4
endogenous mim-1
4
fibroblasts gene
4
gene nonhematopoietic
4
nonhematopoietic cell
4
gene completely
4
silent investigated
4
investigated molecular
4
completely silent
4

Similar Publications