An upstream control region required for inducible transcription of the mouse H1(zero) histone gene during terminal differentiation

Abstract

The replacement linker histone H1 (zero) is associated with terminal differentiation in many mammalian cell types, and its accumulation in chromatin may contribute to transcriptional repression occurring during terminal differentiation. H1 (zero) also accumulates in a variety of cell culture lines undergoing terminal differentiation. During in vitro mouse erythroleukemia cell differentiation, H1 (zero) gene expression is induced very rapidly, prior to the time when the cells actually commit to terminal differentiation. We have used a combination of transfection assays and in vitro DNA-protein interaction studies to identify nuclear protein binding sites in the H1 (zero) promoter that control expression and induction of the H1(zero) gene in mouse erythroleukemia cells. The results indicate that transcription of the H1 (zero) gene is controlled by three elements present in the upstream region of the promoter between positions -305 and -470. Site-directed mutagenesis of each of these elements showed that one of them controls inducibility of the gene in differentiating cells. The other two elements in the upstream control region affect primarily the level of transcription of the gene in undifferentiated and differentiating cells. These two elements share a DNA sequence motif consisting of a (dG)6 tract contained in an eight-base consensus, (A/C)GGGGGG(A/C). Additional copies of this motif are present elsewhere in the H1 (zero) promoter.