Nucleic Acids Research Advance Access originally published online on March 29, 2008
Nucleic Acids Research 2008 36(9):2852-2863; doi:10.1093/nar/gkn098
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Nucleic Acids Research, 2008, Vol. 36, No. 9 2852-2863
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Characterization of Drosophila melanogaster JmjC+N histone demethylases
1Institute of Molecular Biology of Barcelona, CSIC, and Institute for Research in Biomedicine (IRB Barcelona), Parc Científic de Barcelona, Josep Samitier, 1-5. 08028 Barcelona, Spain and 2ICREA
*To whom correspondence should be addressed. Tel: +349 3 403 4958; Fax: +349 3 403 4979; Email: fambmc{at}ibmb.csic.es
Received December 21, 2007. Revised February 14, 2008. Accepted February 20, 2008.
In this article, we characterize histone demethylase activity of the entire family of JmjC+N proteins of Drosophila melanogaster. Our results show that Lid (little imaginal discs), which is structurally homologous to JARID1, demethylates H3K4me3. However, contrary to what would be inferred from its demethylase activity, lid contributes to the establishment of transcriptionally competent chromatin states as: (i) is required for histone H3 acetylation; (ii) contributes to expression of the homoeotic gene Ultrabithorax (Ubx); and (iii) antagonizes heterochromatin-mediated gene silencing (PEV). These results, which are consistent with the identification of lid as a trithorax group (trxG) gene, are discussed in the context of current models for the contribution of H3K4me3 to the regulation of gene expression. Here, we also show that the two Drosophila JMJD2 homologues, dJMJD2(1)/CG15835 and dJMJD2(2)/CG33182, are capable of demethylating both H3K9me3 and H3K36me3. dJMJD2(1)/CG15835 regulates heterochromatin organization, as its over-expression induces spreading of HP1, out of heterochromatin, into euchromatin, without affecting the actual pattern of histone modifications of heterochromatin. dJMJD2(1)/CG15835 is excluded from heterochromatin and localizes to multiple euchromatic sites, where it regulates H3K36 methylation. These results indicate that dJMJD2(1)/CG15835 contributes to delimit hetero- and euchromatic territories through the regulation of H3K36 methylation in euchromatin. On the other hand, dJARID2/CG3654 shows no demethylase activity on H3K4me3, H3K9me3, H3K27me3, H3K36me3 and H4K20me3.
Present address: Clément Carré, RNA Interference and Chromatin Regulation Group, Centre for Genomic Regulation (CRG), PRBB, C/Dr. Aiguader, 88, 08003 Barcelona, Spain
Natalia de Olano, Department of Cellular Biology, School of Medicine, University of Barcelona, Casanova, 143. 08036 Barcelona, Spain
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