¹Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP. UMR7104, 1 Rue Laurent Fries, Illkirch Cédex, France

Correspondence: Dr I Davidson, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP. UMR7104, 1 Rue Laurent Fries, Illkirch Cédex 67404, France. E-mail: irwin@titus.u-strasbg.fr

Received 5 December 2006; Revised 29 May 2007; Accepted 7 June 2007; Published online 16 July 2007.

Abstract

To evaluate the role of murine TFIID subunit TAF4 in activation of cellular genes by all-trans retinoic acid (T-RA), we have characterized the T-RA response of taf4^lox/- and taf4^-/- embryonic fibroblasts. T-RA regulates almost 1000 genes in taf4^lox/- cells, but less than 300 in taf4^-/- cells showing that TAF4 is required for T-RA regulation of most, but not all cellular genes. We further show that T-RA-treated taf4^lox/- cells exhibit transforming growth factor (TGF)-dependent autocrine growth and identify a set of genes regulated by loss of TAF4 and by T-RA corresponding to key mediators of the TGF signalling pathway. T-RA rapidly and potently induces expression of connective tissue growth factor (CTGF) via a conserved DR2 type response element in its proximal promoter leading to serum-free autocrine growth. These results highlight the role of TAF4 as a cofactor in the cellular response to T-RA and identify the genetic programme of a novel cross talk between the T-RA and TGF pathways that leads to deregulated cell growth.