The glucocorticoid receptor binds to a sequence overlapping the TATA box of the human osteocalcin promoter: a potential mechanism for negative regulation.
Expression of the human osteocalcin promoter is negatively regulated by glucocorticoids in vivo. In vitro DNase I and exonuclease III footprinting analysis showed binding of purified glucocorticoid receptor in close proximity to and overlapping with the TATA box of the osteocalcin gene. These results imply competition or interference with binding of the TATA box-binding transcription factor IID as a mechanism of repression of this gene by glucocorticoids. In support of this notion, point mutation analysis of the receptor binding site indicated that flanking nucleotides and not the TATA box motif per se were important for receptor interaction. Moreover, DNA binding competition assays showed specific binding of the receptor only to the TATA box region of the osteocalcin gene and not to the corresponding region of an immunoglobulin heavy-chain promoter.
Strömstedt
P E
PE
Karolinska Institute, Department of Medical Nutrition, Huddinge University Hospital, Sweden.
Poellinger
L
L
Gustafsson
J A
JA
Carlstedt-Duke
J
J
D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D003850:Deoxyribonuclease I; D005090:Exodeoxyribonucleases; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009710:Nucleotide Mapping; D015675:Osteocalcin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D016385:TATA Box; D014158:Transcription, Genetic
D011965:Receptors, Glucocorticoid; D015675:Osteocalcin; D005090:Exodeoxyribonucleases; C020133:exodeoxyribonuclease III; D003850:Deoxyribonuclease I