TAILIEUCHUNG - 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

Levels of deoxyribonuclease I (DNase I) activityin vivo have been shown to be altered by physiological and⁄or pathological processes. However, no information is available on the regulation of DNase I gene (DNASE1) expressionin vivo orin vitro. We first mapped the transcription start sites ofDNASE1in human pancreas and in the DNase I-producing human pan-creatic cancer cell line QGP-1, and revealed a novel site 12 kb upstream of exon 1, which was previously believed to be the single transcription-starting exon. . | iFEBS Journal 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 Yoshihiko Kominato1 Misuzu Ueki2 Reiko Iida3 Yasuyuki Kawai4 Tamiko Nakajima1 Chikako Makita1 Masako Itoi1 Yutaka Tajima1 Koichiro Kishi1 and Toshihiro Yasuda2 1 Department of LegalMedicine and MedicalGenetics Gunma University Japan 2 Division of MedicalGenetics and Biochemistry University of Fukui Japan 3 Division of LegalMedicine University of Fukui Japan 4 Third Division of InternalMedicine University of Fukui Japan Keywords alternative splicing deoxyribonuclease I genes promoter Sp1 Correspondence T. Yasuda Division of Medical Genetics and Biochemistry Faculty of MedicalSciences University of Fukui Eiheiji Fukui 910-1193 Japan Fax 81 776 61 8149 Tel 81 776 61 8287 E-mail tyasuda@ Database The nucleotide sequences reported here have been submitted to the GenBank EMBL DDBJ Data Bank with accession numbers AB188151 and AB188152 Received 22 March 2006 revised 8 May 2006 accepted 15 May 2006 doi Levels of deoxyribonuclease I DNase I activity in vivo have been shown to be altered by physiological and or pathological processes. However no information is available on the regulation of DNase I gene DNASE1 expression in vivo or in vitro. We first mapped the transcription start sites of DNASE1 in human pancreas and in the DNase I-producing human pancreatic cancer cell line QGP-1 and revealed a novel site 12 kb upstream of exon 1 which was previously believed to be the single transcriptionstarting exon. This initiation site marks an alternative starting exon designated 1a. Exons 1 and 1a were used simultaneously as transcriptionstarting exons in pancreas and QGP-1 cells. Promoter assay EMSA and chromatin immunoprecipitation analysis with QGP-1 cells showed the promoter region of exon 1a in which the Sp1 transcription .

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