Abstract
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.
Highlights
-Trace protein (TP)1 is a component of human cerebrospinal fluid (CSF) and one of very few proteins found in CSF not present in serum
Gene [39], which is active in the choroid plexus [40], and to the -LH gene, which is active in the CNS [38]
The human TP gene is regulated by thyroid hormone receptors (TR) in a T3-dependent manner
Summary
-Trace protein (TP) is a component of human cerebrospinal fluid (CSF) and one of very few proteins found in CSF not present in serum. In human CSF, TP is present at 2.6 mg/dl, ranking it among the major CSF proteins [1]. A protein with similar distribution to TP has been identified as prostaglandin D2 synthase (PDS) in rats [6, 7]. TP and PDS were shown to be the same protein [10, 11]. Lipocalins are secretory proteins that transport hydrophobic ligands [13, 14]. In previous work we localized the human TP gene to the lipocalin gene cluster on 9q34. The TP gene bears a striking resemblance to other lipocalin genes, suggesting a role for TP in transport [12]
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