THYROID-HORMONE RECEPTORS BIND TO THE PROMOTER OF THE MOUSE HISTONE H1(0) GENE AND MODULATE ITS TRANSCRIPTION

It has been shown that the mouse histone H1(0) promoter contains a DNA element, composed of a direct repeat of the sequence GGTGACC separate d by 7 nt, which is able to bind retinoic acid receptors and to modula te transcription of reporter genes following treatment with retinoic a cid, We have now investigated whether this DNA motif is also responsiv e to thyroid hormone, We co-transfected CV-1 monkey kidney cells with chloramphenicol acetyltransferase (CAT) expression plasmids containing either 740 bp of the H1(0) wild-type promoter or five copies of the r epeat element cloned in front of the thymidine kinase promoter and exp ression vectors for human thyroid hormone receptors (TRs) a or beta an d retinoid X receptor alpha (RXR alpha). Treatment of transfected cell s with triiodothyronine led to a dose-dependent increase in CAT activi ty, Transfection experiments with increasing amounts of expression vec tors for either TR alpha or RXR alpha resulted in up to g-fold enhance ment of CAT transcription, Furthermore, point mutations within the hal f-sites of the response element of the H1(0) promoter, as well as dele tions within the interspace region, lowered CAT activity to 60-80% of that of the wild-type control, Electrophoretic mobility shift assays s howed that the repeat element was able to form retarded complexes with TR alpha homodimers, as well as with TR alpha-RXR alpha heterodimers. Our results suggest that thyroid hormone receptors are involved in th e regulation of mouse histone H1(0) expression.