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First published online 11 July 2007
doi: 10.1242/dev.005041

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The TFIID subunit TAF4 regulates keratinocyte proliferation and has cell-autonomous and non-cell-autonomous tumour suppressor activity in mouse epidermis

Anas Fadloun¹, Dominique Kobi¹, Jean-Christophe Pointud^1,*, Arup Kumar Indra^1,, Marius Teletin¹, Christine Bole-Feysot¹, Barbara Testoni², Roberto Mantovani², Daniel Metzger¹, Gabrielle Mengus¹ and Irwin Davidson^1,

¹ Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, 67404 Illkirch Cédex, France.
² Dipartimento di Scienze Biomolecolari e Biotecnologie, U. di Milano, Milano, Italy.

Author for correspondence (e-mail: irwin{at}titus.u-strasbg.fr)

Accepted 30 May 2007

The TAF4 subunit of transcription factor TFIID was inactivated in the basal keratinocytes of foetal and adult mouse epidermis. Loss of TAF4 in the foetal epidermis results in reduced expression of the genes required for skin barrier function, leading to early neonatal death. By contrast, TAF4 inactivation in adult epidermis leads to extensive fur loss and an aberrant hair cycle characterised by a defective anagen phase. Although the mutant epidermis contains few normal anagen-phase hair follicles, many genes expressed at this stage are strongly upregulated indicating desynchronised and inappropriate gene expression. The TAF4 mutant adult epidermis also displays interfollicular hyperplasia associated with a potent upregulation of several members of the EGF family of mitogens. Moreover, loss of TAF4 leads to malignant transformation of chemically induced papillomas and the appearance of invasive melanocytic tumours. Together, our results show that TAF4 is an important regulator of keratinocyte proliferation and has cell-autonomous and non-cell-autonomous tumour suppressor activity.

Key words: Alopecia, Hair cycle, Growth factors, EGF, TPA, Wnt pathway, Homologous recombination

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