C/EBPbeta induces chromatin opening at a cell-type-specific enhancer.
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.
Plachetka
Annette
A
Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, D-48149 Münster, Germany.
Chayka
Olesya
O
Wilczek
Carola
C
Melnik
Svitlana
S
Bonifer
Constanze
C
Klempnauer
Karl-Heinz
KH
D000123:Acetyltransferases / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000502:physiology*; D002460:Cell Line / Q000378:metabolism; D002645:Chickens; D002843:Chromatin / Q000235:genetics / Q000648:ultrastructure*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D008969:Molecular Sequence Data; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology*; D038042:Myelopoiesis / Q000235:genetics*; D020626:Oncogene Proteins v-myb / Q000502:physiology; D017434:Protein Structure, Tertiary; D020598:Proto-Oncogene Proteins c-myb / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D017384:Sequence Deletion; D015533:Transcriptional Activation
D022782:CCAAT-Enhancer-Binding Protein-beta; D002843:Chromatin; D020626:Oncogene Proteins v-myb; D020598:Proto-Oncogene Proteins c-myb; D011993:Recombinant Fusion Proteins; D000123:Acetyltransferases; C077509:mim-1 protein, Gallus gallus