Nucleic Acids Research, 1995, Vol. 23, No. 24 5034-5040
© 1995
Articles |
Thyroid hormone receptors bind to the promoter of the mouse historn H10 gene and modulate its transcription
Deutsches Krebsforschungszentrum, Forschugsschwerpunkt Angewandte Tumorvirologie Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
*To whom correspondence should be addressed
Received August 8, 1995. Accepted November 7, 1995.
It has been shown that the mouse histone H1° promoter contains a DNA element, composed of a direct repeat of the sequence GGTGACC separated by 7 nt, which is able to bind retlnoic acid receptors and to modulate transcription of reporter genes following treatment with retlnoic acid. We have now Investigated whether this DNA motif is also responsive to thyroid hormone. We co-transfected CV-1 monkey kidney cells with chloramphenicol acetyftransferase (CAT) expression plasmids containing either 740 bp of the H1° wild-type promoter or five copies of the repeat element cloned in front of the thymidine kinase promoter and expression vectors for human thyroid hormone receptors (TRs) 
or ß and retinoid X receptor a (RXRa). Treatment of transfected cells with triiodothyronine led to a dose-dependent Increase In CAT activity. Transfection experiments with increasing amounts of expression vectors for either TRa or RXRa resulted in up to 6-fold enhancement of CAT transcription. Furthermore, point mutations within the half-sites of the response element of the H1° promoter, as well as deletions within the Interspace region, lowered CAT activity to 60-80% of that of the wild-type control. Electrophoretic mobility shift assays showed that the repeat element was able to form retarded complexes with TR homodimers, as well as with TR-RXR heterodimers. Our results suggest that thyroid hormone receptors are involved in the regulation of mouse histone H1° expression.