Lloret-Llinares Marta, Carré Clément, Vaquero Alejandro, de Olano Natalia, Azorín Fernando
Institute of Molecular Biology of Barcelona, CSIC, Institute for Research in Biomedicine (IRB Barcelona), Parc Científic de Barcelona, Josep Samitier, 1-5, 08028 Barcelona, Spain.
Nucleic Acids Res. 2008 May;36(9):2852-63. doi: 10.1093/nar/gkn098. Epub 2008 Mar 29.
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.
在本文中，我们对黑腹果蝇整个JmjC+N蛋白家族的组蛋白去甲基化酶活性进行了表征。我们的结果表明，与JARID1结构同源的Lid（小成虫盘）可使H3K4me3去甲基化。然而，与其去甲基化酶活性所推断的情况相反，Lid有助于建立转录活性染色质状态，具体表现为：（i）是组蛋白H3乙酰化所必需的；（ii）有助于同源异型基因超双胸（Ubx）的表达；（iii）拮抗异染色质介导的基因沉默（PEV）。这些结果与将Lid鉴定为三胸复合物（trxG）基因的结果一致，并在当前关于H3K4me3对基因表达调控作用的模型背景下进行了讨论。在此，我们还表明，果蝇的两个JMJD2同源物dJMJD2(1)/CG15835和dJMJD2(2)/CG33182能够使H3K9me3和H3K36me3去甲基化。dJMJD2(1)/CG15835调节异染色质组织，因为其过表达会诱导异染色质蛋白1（HP1）从异染色质扩散到常染色质中，而不影响异染色质组蛋白修饰的实际模式。dJMJD2(1)/CG15835被排除在异染色质之外，并定位于多个常染色质位点，在那里它调节H3K36甲基化。这些结果表明，dJMJD2(1)/CG15835通过调节常染色质中的H3K36甲基化，有助于界定异染色质和常染色质区域。另一方面，dJARID2/CG3654对H3K4me3、H3K9me3、H3K27me3、H3K36me3和H4K20me3没有去甲基化酶活性。
