Transcriptional regulation by triiodothyronine requires synergistic action of the thyroid receptor with another trans-acting factor.
Human placental lactogen B (hCS-B) promoter activity is strongly stimulated by triiodothyronine (T3) in pituitary GC cells through interaction between the thyroid receptor and a thyroid receptor-binding element (TBE) spanning coordinates -67 to -41. This TBE is adjacent to the binding site for pituitary factor GHF1 (-95 to -68) which seems necessary for T3 stimulation of hCS-B promoter activity (M. L. Voz, B. Peers, A. Belayew, and J. A. Martial, J. Biol. Chem. 266:13397-13404, 1991). We here demonstrate actual synergy between the thyroid receptor and GHF1. Indeed, in placental JEG-3 cells devoid of factor GHF1, hCS promoter activity is barely stimulated by T3, while a strong response is observed in pituitary GC cells. In the latter, furthermore, neither the TBE nor the GHF1-binding site alone is sufficient to render the thymidine kinase promoter responsive to T3, while in combination they promote strong T3 stimulation. Close proximity between these sites is required for optimal synergy: T3 stimulation globally decreases with increased spacing. Furthermore, synergy occurs not only with a GHF1-binding site but also with all other factor recognition sequences tested (Sp1, NF1, CP1, Oct1, and CACCC boxes) and even with two other copies of the TBE. Nor is it specific to hCS TBE, since the palindromic sequence TCAGGTCA TGACCTGA (TREpal) also exhibits cooperativity.
Voz
M L
ML
Laboratoire de Biologie Moléculaire et de Génie Génétique, Institut de Chimie B6, Université de Liège, Sart-Tilman, Belgium.
Peers
B
B
Wiedig
M J
MJ
Jacquemin
P
P
Belayew
A
A
Martial
J A
JA
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D013961:Thyroid Gland / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000378:metabolism / Q000502:physiology*
D004268:DNA-Binding Proteins; C494186:Pou1f1 protein, rat; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D014284:Triiodothyronine; D004247:DNA