Zaballos Miguel Angel, Cantero Walter, Azpiazu Natalia
Centro de Biología Molecular "Severo Ochoa" CSIC-UAM, C/ Nicolás Cabrera, 1 Universidad Autónoma de Madrid, Madrid, Spain.
PLoS One. 2015 Mar 20;10(3):e0120662. doi: 10.1371/journal.pone.0120662. eCollection 2015.
We have previously identified Homothorax (Hth) as an important factor for the correct assembly of the pericentromeric heterochromatin during the first fast syncytial divisions of the Drosophila embryo. Here we have extended our studies to later stages of embryonic development. We were able to show that hth mutants exhibit a drastic overall reduction in the tri-methylation of H3 in Lys9, with no reduction of the previous di-methylation. One phenotypic outcome of such a reduction is a genome instability visualized by the many DNA breaks observed in the mutant nuclei. Moreover, loss of Hth leads to the opening of closed heterochromatic regions, including the rDNA genomic region. Our data show that the satellite repeats get transcribed in wild type embryos and that this transcription depends on the presence of Hth, which binds to them as well as to the rDNA region. This work indicates that there is an important role of transcription of non-coding RNAs for constitutive heterochromatin assembly in the Drosophila embryo, and suggests that Hth plays an important role in this process.
我们之前已确定同胸蛋白(Hth)是果蝇胚胎首次快速合胞体分裂期间着丝粒周围异染色质正确组装的重要因素。在此,我们将研究扩展至胚胎发育的后期阶段。我们能够证明,hth突变体中赖氨酸9处的组蛋白H3三甲基化显著整体减少,而之前的二甲基化没有减少。这种减少的一个表型结果是基因组不稳定,这在突变细胞核中观察到的许多DNA断裂中得以体现。此外,Hth的缺失导致包括rDNA基因组区域在内的封闭异染色质区域开放。我们的数据表明,卫星重复序列在野生型胚胎中会转录,且这种转录依赖于Hth的存在,Hth会与它们以及rDNA区域结合。这项工作表明,非编码RNA的转录在果蝇胚胎组成型异染色质组装中具有重要作用,并表明Hth在此过程中发挥重要作用。