Intracellular receptor concentration limits glucocorticoid-dependent enhancer activity.
The glucocorticoid receptor protein, in association with cognate hormonal ligands, binds with high affinity to specific DNA sequences termed glucocorticoid response elements (GREs) which can function as hormone-dependent transcriptional enhancers; thus, the receptor is a regulable enhancer-activating protein. We have constructed cell lines expressing different levels of glucocorticoid receptor, and demonstrate that the extent of a structural alteration in the chromatin at a characterized GRE, as well as the magnitude of several transcriptional responses elicited by the receptor, are roughly proportional to the number of receptor molecules per cell. Thus, for three independent glucocorticoid-responsive transcription units examined in our HTC-derived cell lines, the receptor appears to be a primary regulatory factor. Moreover, the results suggest that other cellular factors required for the assembly and function of GREs and transcription initiation complexes must be produced in excess relative to their levels of utilization at normal receptor concentrations.
Vanderbilt
J N
JN
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.
Miesfeld
R
R
Maler
B A
BA
Yamamoto
K R
KR
D002460:Cell Line; D004247:DNA / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000032:analysis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity; D004742:Enhancer Elements, Genetic / Q000187:drug effects*; D008324:Mammary Tumor Virus, Mouse / Q000187:drug effects; D008969:Molecular Sequence Data; D011965:Receptors, Glucocorticoid / Q000032:analysis*
D011965:Receptors, Glucocorticoid; D004247:DNA; D003850:Deoxyribonuclease I