Department of Biology, Drexel University, Philadelphia, PA 19104, USA.
Gene. 2010 Jan 15;450(1-2):8-17. doi: 10.1016/j.gene.2009.09.007.
Histone methylation plays an important role in regulating chromatin-mediated gene control and epigenetic-based memory systems that direct cell fate. Enzymes termed histone demethylases directly remove the methyl marks from histones, thus contributing to a dynamically regulated histone methylated genome; however, the biological functions of these newly identified enzymes remain unclear. The JMJD2A-D family belongs to the JmjC domain-containing family of histone demethylases (JHDMs). Here, we report the cloning and functional characterization of the Drosophila HDM gene Dmel\Kdm4A that is a homolog of the human JMJD2 family. We show that homologs for three human JHDM families, JHDM1, JHDM2, and JMJD2, are present in Drosophila and that each is expressed during the Drosophila lifecycle. Disruption of Dmel\Kdm4A results in a reduction of the male life span and a male-specific wing extension/twitching phenotype that occurs in response to other males and is reminiscent of an inter-male courtship phenotype involving the courtship song. Remarkably, certain genes associated with each of these phenotypes are significantly downregulated in response to Dmel\Kdm4A loss, most notably the longevity associated Hsp22 gene and the male sex-determination fruitless gene. Our results have implications for the role of the epigenetic regulator Dmel\Kdm4A in the control of genes involved in life span and male-specific sex determination in the fly.
组蛋白甲基化在调节染色质介导的基因控制和指导细胞命运的基于表观遗传的记忆系统中发挥重要作用。称为组蛋白去甲基化酶的酶直接从组蛋白上去除甲基标记，从而有助于动态调节的组蛋白甲基化基因组；然而，这些新鉴定的酶的生物学功能仍不清楚。JMJD2A-D 家族属于组蛋白去甲基酶 (JHDM) 的 JmjC 结构域家族。在这里，我们报告了果蝇 HDM 基因 Dmel\Kdm4A 的克隆和功能特征，该基因是人类 JMJD2 家族的同源物。我们表明，三种人类 JHDM 家族（JHDM1、JHDM2 和 JMJD2）的同源物存在于果蝇中，并且在果蝇生命周期中表达。Dmel\Kdm4A 的破坏导致雄性寿命缩短和雄性特异性翅膀延伸/抽搐表型，该表型响应其他雄性而发生，类似于涉及求爱歌曲的雄性间求爱表型。值得注意的是，与每种表型相关的某些基因在 Dmel\Kdm4A 缺失时显著下调，尤其是与长寿相关的 Hsp22 基因和雄性性别决定无果基因。我们的结果表明，表观遗传调节剂 Dmel\Kdm4A 在控制与寿命和雄性特异性性别决定相关的基因方面发挥作用。
