Beta-trace gene expression is regulated by a core promoter and a distal thyroid hormone response element.
We isolated and characterized the human beta-Trace protein (betaTP) gene promoter. betaTP, also known as prostaglandin D2 synthase, is a lipocalin secreted from the choroid plexus and meninges into cerebrospinal fluid. Basal transcription of the betaTP gene is directed from a core promoter found within the first 325 bases of the 5'-flanking sequence. The betaTP gene promoter is responsive to thyroid hormone (3,3',5-triiodothyronine, T3) and efficiently repressed by unliganded human thyroid hormone receptor beta (TRbeta). Functional analysis of the betaTP promoter in TE671 cells revealed that responsiveness to T3 occurs in sequences 2.5 kilobase pairs 5' of the start site. Within the hormone-responsive region we identified a thyroid hormone response element (TRE) located from -2576 to -2562 base pairs relative to the transcription start site. The betaTP TRE is composed of two directly repeated consensus half-sites separated by a 3-base pair space (DR3). The betaTP TRE forms specific complexes with TRbeta. We have shown that a gene active in the choroid plexus and meninges is responsive to T3. T3 may play a role in the regulated transport of substances into the cerebrospinal fluid and ultimately the brain.
White
D M
DM
Department of Neurology and the Brain Research Institute, Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA. dwhite@drugs.bsd.uchicago.edu
Takeda
T
T
DeGroot
L J
LJ
Stefansson
K
K
Arnason
B G
BG
D001483:Base Sequence; D001609:Beta-Globulins / Q000235:genetics*; D003001:Cloning, Molecular; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D019746:Intramolecular Oxidoreductases; D054834:Lipocalins; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*; D013963:Thyroid Hormones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001609:Beta-Globulins; D054834:Lipocalins; D013963:Thyroid Hormones; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase