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

Abstract:

: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.

journal_name

Mol Cell Endocrinol

authors

Van Reeth T,Gabant P,Szpirer C,Szpirer J

doi

10.1016/s0303-7207(01)00739-0

keywords:

subject

Has Abstract

pub_date

2002-02-25 00:00:00

pages

99-109

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303720701007390

journal_volume

188

pub_type

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