The Evolution of the Differentiation-Specific Histone H1 Gene Basal Promoter

Abstract.

The comparison of the rat H1⁰ gene promoter sequence with that of known H1⁰ genes showed a high evolutionary conservation of regulatory elements involved in the control of the basal transcription of the gene. This finding suggests that the regulation of H1⁰ gene expression is also controlled by a very conserved mechanism within vertebrates. In order to confirm this hypothesis, we destroyed three major cis-acting elements in the H1⁰ gene promoter by site-directed mutagenesis and showed that these mutations affect significantly the activity of this promoter in cell lines representative of different vertebrate classes (fishes, amphibians, reptiles, birds, and mammals). We concluded that H1⁰ gene activity, which is a developmentally regulated process, has been under a great selective pressure during evolution to ensure the expression of the protein at crucial periods of vertebrate development. One of these elements, the H4 box, helps to define within vertebrate H1 genes those encoding differentiation-specific subtypes. Indeed, it is only present in the proximal promoter region of H1⁰ and H5 encoding genes. Regarding this feature of the vertebrate differentiation-specific H1 genes, they appear closer to the invertebrate (sea urchin) H1 genes than to those encoding vertebrate replication-dependent (RD) H1. This observation suggests that histone H1⁰ and H5 are members that diverged from the main group of histone H1 before the vertebrate histone H1 and that the regulation of vertebrate RD H1 genes has probably evolved toward a coordinate regulation with that of core histone genes.