DIFFERENTIAL REGULATION OF THE HUMAN H1-DEGREES-HISTONE-GENE TRANSCRIPTION IN HUMAN TUMOR-CELL LINES

Cloning and sequence analysis of about 2 kb of the 5' flanking region of the human H1-degrees histone gene reveals several potential regulatory elements upstream of the transcribed portion of this gene. Transfection studies using the chloramphenicol acetyl tranferase (CAT) gene as a reporter gene with a series of promoter deletions revealed that the expression of the H1-degrees gene may depend on a complex interplay of several transcription factors, including members of the retinoic acid and/or thyroid-hormone-receptor superfamily, at the 5' flanking region of the H1-degrees gene. CAT assays demonstrate varied patterns of expression and regulation in different human tumor-cell lines. The leukemia cell line HL60 does not express H1-degrees mRNA and shows no CAT activity. HeLa cells strongly express the CAT gene under the control of the H1-degrees promoter. Under the same conditions, HepG2 cells also transcribe the CAT gene, although at a lower rate than HeLa cells. Using different promoter-deletion clones, the CAT activity differs in HepG2 and HeLa cells in the very distal promoter region. In both cell lines, the CAT activity decreases several fold when the region between nucleotides -450 and -600 upstream of the mRNA start site is deleted. It also decreases when just the proximal portion but not the distal promoter region is deleted. In summary, the regulatory patterns of these three cell lines differ, indicating a cell-type-specific regulation of the human H1-degrees-histone-gene expression.