We have isolated genomic clones of the Xenopus laevis histone H1-degrees promoter and identified regulatory elements mediating the transcriptional regulation of the H1-degrees gene. Expression of H1-degrees is associated with the terminal differentiation of many cell types. During X. laevis development, H1-degrees mRNA is present in the oocyte and egg, but remains at low levels during embryogenesis until hatching. After this time, mRNA levels accumulate dramatically correlating with the differentiation of many tissue types, e.g., liver and skin. Accumulation of H1-degrees mRNA can be induced at earlier developmental stages by treating embryos with butyrate. The enhanced transcription of H1-degrees in adult somatic cells, as well as the butyrate inducibility of the gene, have been investigated using transfection of adult X. laevis A6 somatic cells. We have defined specific protein-nucleic acid interactions with three cis-acting elements. Two previously defined gene regulatory elements: the H1 box, normally involved in the regulation of the H1 gene, and the H4TF2 site, normally involved in the regulation of the H4 gene, appear to have novel roles in determining differentiation-specific H1-degrees expression. These two elements act together with a new distal cis-acting element in order to sustain high levels of basal transcription and to potentiate transcription following butyrate treatment.