THE RAT HEPATIC LEUKEMIA FACTOR (HLF) GENE ENCODES 2 TRANSCRIPTIONAL ACTIVATORS WITH DISTINCT CIRCADIAN-RHYTHMS, TISSUE DISTRIBUTIONS AND TARGET PREFERENCES

Hepatic leukemia factor (HLF) is a member of the PAR family of transcr iption regulatory proteins. We have characterized the rat HLF gene and studied its expression and activity. The rat HLF gene is transcribed from two alternative promoters, alpha and beta, with different circadi an amplitudes and tissue specificities. The alpha RNA isoforms produce a 43 kDa protein, HLF43, abundant in brain, liver and kidney, like th e previously described human HLF RNA. The beta RNA HLF isoforms use a CUG codon to initiate translation of a novel 36 kDa protein, HLF36, wh ich is shorter at its N-terminus relative to the 43 kDa form. HLF36 is expressed uniquely in the liver, where it is the most abundant HLF pr otein. Surprisingly, the two proteins accumulate in the liver with dif ferent circadian amplitudes and have distinct liver-specific promoter preferences in transfection experiments. Thus, HLF43 stimulates transc ription from the cholesterol 7 alpha-hydroxylase promoter much more ef ficiently than from the albumin promoter, while the converse is true f or HLF36.