BETA-TRACE GENE-EXPRESSION IS REGULATED BY A CORE PROMOTER AND A DISTAL THYROID-HORMONE RESPONSE ELEMENT

We isolated and characterized the human P-Trace protein (beta TP) gene promoter. beta TP, also known as prostaglandin D-2 synthase, is a lip ocalin secreted from the choroid plexus and meninges into cerebrospina l fluid. Basal transcription of the beta TP gene is directed from a co re promoter found within the first 325 bases of the 5'-flanking sequen ce. The beta TP gene promoter is responsive to thyroid hormone (3,3',5 triiodothyronine, T-3) and efficiently repressed by unliganded human thyroid hormone receptor beta (TR beta, Functional analysis of the bet a TP promoter in TE671 cells revealed that responsiveness to T-3 occur s in sequences 2.5 kilobase pairs 5' of the start site, Within the hor mone-responsive region we identified a thyroid hormone response elemen t (TRE) located from -2576 to -2562 base pairs relative to the transcr iption start site. The beta TP TRE is composed of two directly repeate d consensus half-sites separated by a 3-base pair space (DR3). The bet a TP TRE forms specific complexes with TR beta, We have shown that a g ene active in the choroid plexus and meninges is responsive to T-3. T- 3 may play a role in the regulated transport of substances into the ce rebrospinal fluid and ultimately the brain.