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Molecular and Cellular Biology, March 2003, p. 1808-1816, Vol. 23, No. 5
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.5.1808-1816.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Cascade of Distinct Histone Modifications during Collagenase Gene Activation

Joost H. A. Martens, Matty Verlaan, Eric Kalkhoven, and Alt Zantema*

Molecular Cell Biology, Leiden University Medical Center, 2300 RA Leiden, The Netherlands,

Received 16 September 2002/ Returned for modification 13 November 2002/ Accepted 10 December 2002

Gene activation in eukaryotes requires chromatin remodeling, in part via histone modifications. To study the events at the promoter of a mitogen-inducible gene, we examined the induction of expression of the collagenase gene. It has been established that the collagenase gene can be activated by c-Jun and c-Fos and that the transcriptional coactivator p300 is involved in the activation. As expected, we found histone acetyltransferase activity at the collagenase promoter during activation. Interestingly, we also found histone methyltransferase and kinase activity. Strikingly, the first modification observed is methylation of histone H3 lysine 4, which correlates with the binding of the SET9 methyltransferase and the assembly of a complex consisting of c-Jun, c-Fos, TATA binding protein, and RNA polymerase II. The assembly of the preinitiation complex also shows an ordered binding of the acetyltransferase p300, the RSK2 kinase, and the SWI/SNF component Brg-1. Our results suggest that collagenase gene activation involves a dynamic recruitment of different factors and that in addition to acetylation, histone H3 lysine 4 di- and trimethylation and histone H3 serine 10 phosphorylation are important steps in the activation of this gene.

* Corresponding author. Mailing address: MCB1, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands. Phone: 31 (0)71 5276113. Fax: 31 (0)71 5276284. E-mail: zantema{at}lumc.nl.

Molecular and Cellular Biology, March 2003, p. 1808-1816, Vol. 23, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.5.1808-1816.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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