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Originally published as MBC in Press, 10.1091/mbc.E09-02-0114 on May 28, 2009

Vol. 20, Issue 15, 3543-3551, August 1, 2009

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Induction of HoxB Transcription by Retinoic Acid Requires Actin Polymerization

Carmelo Ferrai*,{dagger},{ddagger}, Gabriela Naum-Onganía§,{ddagger},||, Elena Longobardi§, Martina Palazzolo*, Andrea Disanza§, Victor M. Diaz*, Massimo P. Crippa*, Giorgio Scita§, and Francesco Blasi*,§

*San Raffaele Scientific Institute and University Vita Salute San Raffaele, 20132 Milan, Italy; and § IFOM, the FIRC Institute of Molecular Oncology Foundation, 20139 Milan, Italy

Submitted February 9, 2009; Revised May 18, 2009; Accepted May 19, 2009
Monitoring Editor: Richard K. Assoian

We have analyzed the role of actin polymerization in retinoic acid (RA)-induced HoxB transcription, which is mediated by the HoxB regulator Prep1. RA induction of the HoxB genes can be prevented by the inhibition of actin polymerization. Importantly, inhibition of actin polymerization specifically affects the transcription of inducible Hox genes, but not that of their transcriptional regulators, the RARs, nor of constitutively expressed, nor of actively transcribed Hox genes. RA treatment induces the recruitment to the HoxB2 gene enhancer of a complex composed of "elongating" RNAPII, Prep1, β-actin, and N-WASP as well as the accessory splicing components p54Nrb and PSF. We show that inhibition of actin polymerization prevents such recruitment. We conclude that inducible Hox genes are selectively sensitive to the inhibition of actin polymerization and that actin polymerization is required for the assembly of a transcription complex on the regulatory region of the Hox genes.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E09-02-0114) on May 28, 2009.

{ddagger} Co-first author.

Present Addresses: {dagger}MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom;

||Centro Regional de Estudios Genómicos (CREG), Florencio Varela (1888), Buenos Aires, Argentina.

Address correspondence to: Francesco Blasi (francesco.blasi{at}ifom-ieo-campus.it)






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