Characterization of the genomic structure and tissue-specific promoter of the human nuclear receptor NR5A2 (hB1F) gene.
The human homologue of the Drosophila melanogaster orphan nuclear receptor fushi tarazu factor 1 (Ftz-F1), NR5A2 (hB1F), was initially identified as a regulatory factor that binds and activates enhancer II of hepatitis B virus. NR5A2 (hB1F) is expressed specifically in pancreas and liver, playing important roles in the regulation of several liver-specific genes. A detailed analysis on the genomic structure and promoter activity will greatly promote future studies on the function of the NR5A2 (hB1F) gene. In this report, a bacterial artificial chromosome clone and several phage clones covering the NR5A2 (hB1F) gene were isolated and the complete genomic sequence was obtained. Alignment of different cDNAs of the NR5A2 (hB1F) gene with the genomic sequence facilitated the delineation of its structural organization, which spans over 150 kb and consists of eight exons interrupted by seven introns. RT-PCR and 3'-RACE revealed that utilization of two polyadenylation signals results in the 3.8 and 5.2 kb transcripts that were observed previously. The transcription start site of the NR5A2 (hB1F) gene was mapped downstream of a canonical TATA box. An upstream fragment containing binding sites for several liver-specific and ubiquitous transcription factors exhibits hepatocyte-specific promoter activity. Transient transfections indicated that hepatocyte nuclear factors HNF1 and HNF3beta could activate NR5A2 (hB1F) promoter.
Zhang
C K
CK
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, 200031, Shanghai, China.
Lin
W
W
Cai
Y N
YN
Xu
P L
PL
Dong
H
H
Li
M
M
Kong
Y Y
YY
Fu
G
G
Xie
Y H
YH
Huang
G M
GM
Wang
Y
Y
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins; D005091:Exons; D005796:Genes / Q000235:genetics*; D006367:HeLa Cells; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D007438:Introns; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D011061:Poly A / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; C082631:NR5A2 protein, human; D010750:Phosphoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; C501970:Tcfl4 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D011061:Poly A; D004247:DNA; D008156:Luciferases