β-trace gene expression is regulated by a core promoter and a distal thyroid hormone response element

We isolated and characterized the human β-Trace protein (βTP) gene promoter. βTP, also known as prostaglandin D₂ synthase, is a lipocalin secreted from the choroid plexus and meninges into cerebrospinal fluid. Basal transcription of the βTP gene is directed from a core promoter found within the first 325 bases of the 5'-flanking sequence. The βTP gene promoter is responsive to thyroid hormone (3,3',5-triiodothyronine, T₃) and efficiently repressed by unliganded human thyroid hormone receptor β (TRβ). Functional analysis of the βTP 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 βTP TRE is composed of two directly repeated consensus half- sites separated by a 3-base pair space (DR3). The βTP TRE forms specific complexes with TRβ. 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.