Báo cáo khoa học: Characterization of human deoxyribonuclease I gene (DNASE1) promoters reveals the utilization of two transcription-starting exons and the involvement of Sp1 in its transcriptional regulation

Characterization of human deoxyribonuclease I gene (DNASE1) promoters reveals the utilization of two transcription-starting exons and the involvement of Sp1 in its transcriptional regulation

Authors: Yoshihiko Kominato, Misuzu Ueki, Reiko Iida, Yasuyuki Kawai, Tamiko Nakajima, Chikako Makita, Masako Itoi, Yutaka Tajima, Koichiro Kishi and Toshihiro Yasuda

Field: Molecular Medicine and Genetics, Biochemistry

Document Content: This study investigates the regulation of human deoxyribonuclease I (DNase I) gene expression, focusing on its promoter regions and transcriptional factors. Researchers identified a novel transcription-starting exon, designated exon la, located approximately 12 kb upstream of the previously known exon 1. Both exon 1 and exon la were found to be utilized simultaneously as transcription-starting exons in human pancreas and QGP-1 cells. Promoter assays, EMSA, and ChIP analysis indicated that the transcription factor Sp1 plays a crucial role in the promoter activity of the 5′-upstream region of exon la. This marks the first identification of a transcription factor responsible for the gene expression of vertebrate DNase I genes. Furthermore, RT-PCR analysis revealed alternative splicing of human DNASE1 pre-mRNA, with only two of eight identified splicing products capable of producing intact DNase I protein. These findings suggest that human DNASE1 expression is regulated through the combined mechanisms of alternative promoter usage and alternative splicing.

Detailed Table of Contents:

• Keywords
• Correspondence
• Database
• Abstract
• Introduction
• Results
• Discussion
• Experimental Procedures
• Acknowledgements
• References