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Stimulation of the α-fetoprotein promoter by unliganded thyroid hormone receptor in association with protein deacetylation

par Van Reeth, Thierry ;Gabant, Philippe ;Szpirer, Claude ;Szpirer, Josiane
Référence Molecular and cellular endocrinology, 188, 1-2, page (99-109)
Publication Publié, 2002-02

Article révisé par les pairs

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Résumé :

α-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. © 2002 Elsevier Science Ireland Ltd. All rights reserved.