Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
PLoS One. 2012;7(6):e39758. doi: 10.1371/journal.pone.0039758. Epub 2012 Jun 27.
The KDM4 subfamily of JmjC domain-containing demethylases mediates demethylation of histone H3K36me3/me2 and H3K9me3/me2. Several studies have shown that human and yeast KDM4 proteins bind to specific gene promoters and regulate gene expression. However, the genome-wide distribution of KDM4 proteins and the mechanism of genomic-targeting remain elusive. We have previously identified Drosophila KDM4A (dKDM4A) as a histone H3K36me3 demethylase that directly interacts with HP1a. Here, we performed H3K36me3 ChIP-chip analysis in wild type and dkdm4a mutant embryos to identify genes regulated by dKDM4A demethylase activity in vivo. A subset of heterochromatic genes that show increased H3K36me3 levels in dkdm4a mutant embryos overlap with HP1a target genes. More importantly, binding to HP1a is required for dKDM4A-mediated H3K36me3 demethylation at a subset of heterochromatic genes. Collectively, these results show that HP1a functions to target the H3K36 demethylase dKDM4A to heterochromatic genes in Drosophila.
JmjC 结构域包含的 KDM4 亚家族的去甲基酶介导组蛋白 H3K36me3/me2 和 H3K9me3/me2 的去甲基化。几项研究表明，人和酵母的 KDM4 蛋白与特定的基因启动子结合，调节基因表达。然而，KDM4 蛋白的全基因组分布和基因组靶向的机制仍然难以捉摸。我们之前已经鉴定出果蝇 KDM4A（dKDM4A）作为一种组蛋白 H3K36me3 的去甲基酶，它可以直接与 HP1a 相互作用。在这里，我们在野生型和 dkdm4a 突变体胚胎中进行了 H3K36me3 ChIP-chip 分析，以鉴定体内由 dKDM4A 去甲基酶活性调节的基因。在 dkdm4a 突变体胚胎中显示 H3K36me3 水平升高的一组异染色质基因与 HP1a 靶基因重叠。更重要的是，HP1a 的结合对于 dKDM4A 在一组异染色质基因上介导的 H3K36me3 去甲基化是必需的。总之，这些结果表明 HP1a 作为一种将 H3K36 去甲基酶 dKDM4A 靶向果蝇异染色质基因的蛋白发挥作用。
