Abstract: OBJECTIVE: Here we report the cloning and characterization of two novel splice variants of DHRS4L2 gene and potential mechanisms regulating the transcription. METHODS: RT_PCR, 3'_RACE and bioinformatics were used to clone and characterize the novel splice variant of DHRS4L2 from human hepatic immortalized cell line HL_7702. Transcription of DHRS4L2 was investigated by RT_PCR in 5_aza_dC treated HL_7702 and Hep_G2 cell lines. RESULTS: we found two novel splice variants DHRS4L2A and DHRS4L2A3，both with alternative first exon Ea. The former lacked exon 1 and the latter, exon 1 and exon 3. After 5_aza_dC treatments, DHRS4L2 transcripts with first exon E1 were increased in normal hepatic cells while the reverse trend was found in malignant hepatic cells. CONCLUSION: We found two novel splice variants of DHRS4 and suggested that the alternative starts of DHRS4L2 transcription may be regulated by methylation. The effect of methylation is different between normal and malignant cell lines and the underlying mechanism remains to be investigated.

Key words: NADP(H)_dependent retinol dehydrogenase/reductase, transcription regulation, DHRS4L2 gene alternative splicing