Genomewide identification of target genes of histone methyltransferase dG9a during Drosophila embryogenesis
Genomewide identification of target genes of histone methyltransferase dG9a during Drosophila embryogenesis
复制标题
DOI：
10.1111/gtc.12281
复制
发表时间：
2015-11
期刊：
影响因子：
2.1
通讯作者：
Kouhei Shimaji;Takahiro Konishi;Shintaro Tanaka;H. Yoshida;Yasuko Kato;Y. Ohkawa;Tetsuya Sato;M. Suyama;H. Kimura;M. Yamaguchi
中科院分区：
文献类型：
--
作者：
Kouhei Shimaji;Takahiro Konishi;Shintaro Tanaka;H. Yoshida;Yasuko Kato;Y. Ohkawa;Tetsuya Sato;M. Suyama;H. Kimura;M. Yamaguchi
组蛋白的翻译后修饰在各种生物过程的表观遗传调控中发挥着重要作用。在已鉴定的组蛋白甲基转移酶 (HMTase) 中，G9a 是在常染色质区域活跃的组蛋白 H3 Lys 9 (H3K9) 特异性实例。据报道，果蝇 G9a (dG9a) 在体内具有 H3K9 二甲基化活性。在这里，我们发现纯合 dG9a 无效突变体和 dG9a 无效突变体的异等位基因组合的孵化所需的时间被延迟，这表明 dG9a 至少部分负责胚胎发生的进展。对野生型和 dG9a 无效突变果蝇的免疫细胞化学分析表明，dG9a 定位于细胞质中直至核分裂周期 7，其中它可能负责无核小体 H3K9 的二甲基化。从第 8-11 周期，dG9a 进入细胞核并负责核小体中 H3K9 的二甲基化。利用早期野生型和 dG9a 突变胚胎的 RNA 序列分析表明，dG9a 下调负责胚胎发生的基因的表达。 RNA荧光原位杂交分析进一步显示这些mRNA的时间和空间表达模式在dG9a突变体中没有显着变化。这些结果表明dG9a控制一些合子基因的转录水平，而不改变这些基因转录物的时间和空间表达模式。
Post‐translational modification of the histone plays important roles in epigenetic regulation of various biological processes. Among the identified histone methyltransferases (HMTases), G9a is a histone H3 Lys 9 (H3K9)‐specific example active in euchromatic regions. Drosophila G9a (dG9a) has been reported to feature H3K9 dimethylation activity in vivo. Here, we show that the time required for hatching of a homozygous dG9a null mutant and heteroallelic combination of dG9a null mutants is delayed, suggesting that dG9a is at least partially responsible for progression of embryogenesis. Immunocytochemical analyses of the wild‐type and the dG9a null mutant flies indicated that dG9a localizes in cytoplasm up to nuclear division cycle 7 where it is likely responsible for di‐methylation of nucleosome‐free H3K9. From cycles 8–11, dG9a moves into the nucleus and is responsible for di‐methylating H3K9 in nucleosomes. RNA‐sequence analysis utilizing early wild‐type and dG9a mutant embryos showed that dG9a down‐regulates expression of genes responsible for embryogenesis. RNA fluorescent in situ hybridization analysis further showed temporal and spatial expression patterns of these mRNAs did not significantly change in the dG9a mutant. These results indicate that dG9a controls transcription levels of some zygotic genes without changing temporal and spatial expression patterns of the transcripts of these genes.