Stimulation of the alpha-fetoprotein promoter by unliganded thyroid hormone receptor in association with protein deacetylation.
alpha-Fetoprotein (AFP) is a serum protein expressed during fetal life, the expression of which is shut off after birth. The activity of the mouse Afp gene promoter region comprised between -80 and -38 bp is regulated by the thyroid hormone receptor (T3R): negatively in the presence of T3 and positively in the absence of T3. The stimulating effect of unliganded T3R is, unexpectedly, antagonized by cofactors that have histone-acetyl-transferase activity, or by sodium butyrate, which inhibits histone acetylases (HDACs). The unliganded T3R stimulating activity effect is thus associated with protein deacetylation, contrary to the usual situation. In combination with previous results, our observations suggest that T3-mediated down regulation of the Afp promoter is due to T3-induced protein acetylation leading to loss of a nucleosomal structure (required for promoter activity) and chromatin opening.
Van Reeth
Thierry
T
Laboratoire de Biologie du Développement, Dept. de Biologie Moleculaire, IBMM, Université Libre de Bruxelles,Rue Profs. Jeener & Brachet 12, B-6041 Gosselies, Belgium.
Gabant
Philippe
P
Szpirer
Claude
C
Szpirer
Josiane
J
D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000509:alpha-Fetoproteins / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D056572:Histone Deacetylase Inhibitors; D009687:Nuclear Proteins; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D014157:Transcription Factors; D000509:alpha-Fetoproteins; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D008156:Luciferases; D006655:Histone Deacetylases