The rat growth hormone gene contains multiple thyroid response elements

The thyroid hormone receptor exerts transcriptional control over a variety of genes. This report describes four sites that bind this receptor with high affinity within the 5′-flanking DNA of the rat growth hormone gene, approximately centered at −180, −160, −60 and −20 nucleotides from the transcrip...

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Veröffentlicht in:The Journal of biological chemistry 1989-07, Vol.264 (20), p.12063-12073
Hauptverfasser: Norman, M F, Lavin, T N, Baxter, J D, West, B L
Format: Artikel
Sprache:eng
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Zusammenfassung:The thyroid hormone receptor exerts transcriptional control over a variety of genes. This report describes four sites that bind this receptor with high affinity within the 5′-flanking DNA of the rat growth hormone gene, approximately centered at −180, −160, −60 and −20 nucleotides from the transcription start site. These sites were defined by gel retardation of short synthetic oligonucleotides using native receptor purified several hundred-fold from rat liver. Binding sites were also defined by methylation interference and methidium-propyl-EDTA footprinting. Alignment of the four binding sites suggests that each contains two purine-rich regions, the more downstream of which, GGGTACCG, is highly conserved. Mutations made within each of the two upstream sites reduce receptor binding affinity. For one mutation, a partial loss of receptor binding strength correlated with a change in electrophoretic mobility, indicating that receptor binding may alter DNA conformation. Mutations at each of the four sites also reduce thyroid hormone responsiveness of the −237/+11 promoter linked to the chloramphenicol acetyltransferase gene coding sequences and transfected into cultured pituitary (GC) cells. These results suggest that several different receptor-binding elements interact to control thyroid hormone responsiveness of the rat growth hormone gene and reveal common sequences that may be important for receptor-DNA recognition.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)80174-0