Structure and localization of the human gene encoding SR-BI/CLA-1. Evidence for transcriptional control by steroidogenic factor 1.
The scavenger receptor, class B, type 1 receptor (SR-BI) mediates the selective transport of lipids from high density lipoprotein to cells. We describe the structure and subchromosomal location of human SR-BI and provide evidence that it is regulated by the transcription factor, steroidogenic factor 1 (SF-1). SR-BI resides on chromosome 12q24.2-qter, spans approximately 75 kilobase pairs, and contains 13 exons. RNA blot analysis of human tissues reveals an expression pattern similar to that described previously for rodents with the highest levels of mRNA in the adrenal gland, ovary, and liver. Unlike rodents, human SR-BI was expressed at high levels in the placenta. The transcription start site for SR-BI was mapped, and DNA sequence analysis revealed a binding site for SF-1 in the proximal 5'-flanking sequence. SF-1, an orphan member of the nuclear hormone receptor gene family, plays a key role in the regulation of steroidogenesis and is expressed at high levels in steroidogenic tissues. SF-1 binds to the SR-BI promoter in a sequence-specific manner, and efficient transcription from this promoter in adrenocortical Y1 cells is dependent on an intact SF-1 site. These data extend our understanding of SF-1 function within steroidogenic tissues and suggest that SR-BI, which serves to supply selected tissues with lipoprotein-derived lipids, is part of the repertoire of SF-1-responsive genes involved in steroidogenesis.
Cao
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Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
Garcia
C K
CK
Wyne
K L
KL
Schultz
R A
RA
Parker
K L
KL
Hobbs
H H
HH
D001483:Base Sequence; D001692:Biological Transport; D018955:CD36 Antigens / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism; D002881:Chromosomes, Human, Pair 12; D004268:DNA-Binding Proteins / Q000502:physiology*; D005091:Exons; D051717:Fushi Tarazu Transcription Factors; D015723:Gene Library; D018398:Homeodomain Proteins; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000235:genetics*; D051116:Receptors, Scavenger; D015183:Restriction Mapping; D051122:Scavenger Receptors, Class B; D054339:Steroidogenic Factor 1; D014018:Tissue Distribution; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D018955:CD36 Antigens; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D008565:Membrane Proteins; C515057:NR5A1 protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; D002784:Cholesterol