Identification of multiple regulatory elements of human L-histidine decarboxylase gene.
Previously, we reported the structure of human L-histidine decarboxylase gene. To identify the regions that regulate the tissue-specific expression of HDC, we constructed a fusion DNA with the 5'-flanking region from -1003 to +99 of the HDC gene and chloramphenicol acetyltransferase (CAT) gene, which was then transfected into human basophilic leukemia KU-812-F cells or human epithelial carcinoma HeLa cells. The 1102 bp DNA fragment stimulated the CAT activity in KU-812-F cells, but not in HeLa cells. CAT analysis with a series of 5'-deletion constructs of the HDC-CAT gene revealed the existence of two positive and one negative regulatory elements at -855 to -841 and -532 to -497 and -829 to -821, respectively. Sequence analysis showed a nuclear factor c-Myb binding motif, TAACTG, at position -520. Gel mobility shift analysis showed that the nuclear extract of KU-812-F cells, but not that of HeLa cells, contains a factor which can bind to this motif. These results suggest that the 5'-flanking region of the HDC gene contains multiple regulatory elements for HDC gene expression and that at least one element, including a c-Myb binding motif, is responsible for the tissue-specific expression of HDC.
Nakagawa
S
S
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku.
Okaya
Y
Y
Yatsunami
K
K
Tanaka
S
S
Ohtsu
H
H
Fukui
T
T
Watanabe
T
T
Ichikawa
A
A
D001665:Binding Sites; D002457:Cell Extracts / Q000032:analysis; D002467:Cell Nucleus; D016384:Consensus Sequence / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics*; D005796:Genes / Q000235:genetics*; D006367:HeLa Cells / Q000378:metabolism*; D006640:Histidine Decarboxylase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators
D002457:Cell Extracts; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators; D006640:Histidine Decarboxylase