Identity between rat htf and human xbp-1 genes: determination of gene structure, target sequence, and transcription promotion function for HTF

Hepatocarcinogenesis-related transcription factor (HTF) was originally isol ated from rats in which the expression was enhanced in hepatocellular carci nomas. Rat HTF (rHTF) is structurally similar to human X-box-binding protei n-1 (hXBP-1), and both factors are unique in respective genomes. A previous study showed that hXBP-1 mRNA is detectable ubiquitously but is enriched i n the human liver as rHTF. In this study, we demonstrated the analogous exo n-intron organization and significant sequence homology for rhtf and hxbp-1 genes. Alignment of amino acid sequences of rHTF and hXBP-1 revealed that all the characteristic motifs in rHTF were conserved in hXBP-1. Moreover, S outhern blotting patterns provided with the rHTF and hXBP-1 probes were bas ically the same. These two genes were thus thought to belong to the same ev olutional lineage. We determined the consensus binding sequence (CRCGTCA) f or rHTF by CASTing, and it was found to be nearly the same as that for hXBP -1. Transactivation ability of rHTF was also demonstrated. The rhtf gene ge nerates two types of mRNAs (2.0 kb and 2.5 kb), both of which encode identi cal rHTF protein. These transcripts had distinct transcription initiation s ites. The 2.0 kb promoter, that was revealed by the transient luciferase as say, contained GC-box and CAAT-box. Sequences around the transcription init iation site for the 2.0 kb transcript were similar in rhtf and hxbp-1 genes . Our observations suggest that HTF is a rat homolog of hXBP-1. (C) 2000 El sevier Science B.V. All rights reserved.