The genomic structure of the human glucocorticoid receptor.
We have determined the structure of the human glucocorticoid receptor (hGR) gene after the isolation and characterization of cosmid clones mapping to discrete regions of the cDNA. The gene contains a total of 10 exons and has a minimum size of 80 kilobases. Exon 1 consists solely of 5'-untranslated sequence, and exon 2 encodes the amino-terminal portion of the receptor. The two putative zinc fingers are separately encoded by two exons, and a total of five exons combine to form the cortisol-binding domain. By restriction mapping and sequence analysis of cosmids located on the 3'-end of the gene, we have established that the two receptor isoforms, hGR alpha and hGR beta, originate from the same gene by alternative splicing. Each hGR isoform is encoded by nine exons, of which the first eight are identical, whereas the ninth exons are heterologous. Multiple GC boxes and no obvious TATA or CAAT elements have been found in the 5'-flanking region. S1 nuclease analysis yielded one major band, and the transcription start site is localized to the *C residue within TAC*CCTC. Alignment of sequences around the splice junctions of hGR with those of other members of the steroid receptor superfamily revealed three different splice positions within the DNA-binding domain. This comparison also permitted the prediction of the positions of the splice sites and the sizes of the putative exons in the human mineralocorticoid receptor.
Encío
I J
IJ
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland 20892.
Detera-Wadleigh
S D
SD
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D003360:Cosmids; D005091:Exons; D015723:Gene Library; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012326:RNA Splicing; D012333:RNA, Messenger; D011956:Receptors, Cell Surface / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011965:Receptors, Glucocorticoid; D011061:Poly A; D012313:RNA