The mouse
beta-globin gene locus control region (LCR), located upstream of the
beta-globin gene cluster, is essential for the activated transcription of genes in the cluster. The LCR contains multiple binding sites for
transactivators, including Maf-recognition elements (MAREs). However, little is known about the specific
proteins that bind to these sites or the time at which they bind during erythroid differentiation. We have performed
chromatin immunoprecipitation experiments to determine the recruitment of the erythroid-specific
transactivator p45 NF-E2/MafK (p18 NF-E2) heterodimer and small
Maf proteins to various regions in the
globin gene locus before and after the induction of murine
erythroleukemia (MEL) cell differentiation. We report that, before induction, the LCR is occupied by small
Maf proteins, and, on erythroid maturation, the NF-E2 complex is recruited to the LCR and the active
globin promoters, even though the promoters do not contain MAREs. This differentiation-coupled recruitment of NF-E2 complex correlates with a greater than 100-fold increase in beta-major
globin transcription, but is not associated with a significant change in locus-wide
histone H3 acetylation. These findings suggest that the
beta-globin gene locus exists in a constitutively open
chromatin conformation before terminal differentiation, and we speculate that recruitment of NF-E2 complex to the LCR and active promoters may be a rate-limiting step in the activation of
beta-globin gene expression.