Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Nucleic Acids Res. 2018 Dec 14;46(22):11743-11758. doi: 10.1093/nar/gky892.
Eyeless (ey) is one of the most critical transcription factors for initiating the entire eye development in Drosophila. However, the molecular mechanisms through which Ey regulates target genes and pathways have not been characterized at the genomic level. Using ChIP-Seq, we generated an endogenous Ey-binding profile in Drosophila developing eyes. We found that Ey binding occurred more frequently at promoter compared to non-promoter regions. Ey promoter binding was correlated with the active transcription of genes involved in development and transcription regulation. An integrative analysis revealed that Ey directly regulated a broad and highly connected genetic network, including many essential patterning pathways, and known and novel eye genes. Interestingly, we observed that Ey could target multiple components of the same pathway, which might enhance its control of these pathways during eye development. In addition to protein-coding genes, we discovered Ey also targeted non-coding RNAs, which represents a new regulatory mechanism employed by Ey. These findings suggest that Ey could use multiple molecular mechanisms to regulate target gene expression and pathway function, which might enable Ey to exhibit a greater flexibility in controlling different processes during eye development.
无眼（ey）是果蝇中启动整个眼睛发育的最重要的转录因子之一。然而，Ey 调节靶基因和途径的分子机制尚未在基因组水平上得到描述。我们使用 ChIP-Seq 在果蝇发育的眼睛中生成了内源性 Ey 结合图谱。我们发现，与非启动子区域相比，Ey 结合更频繁地发生在启动子上。Ey 启动子结合与参与发育和转录调控的基因的活性转录相关。综合分析表明，Ey 直接调节一个广泛而高度连接的遗传网络，包括许多重要的模式形成途径以及已知和新的眼睛基因。有趣的是，我们观察到 Ey 可以针对同一途径的多个组件，这可能在眼睛发育过程中增强其对这些途径的控制。除了蛋白质编码基因，我们还发现 Ey 还靶向非编码 RNA，这代表 Ey 采用的一种新的调控机制。这些发现表明，Ey 可以使用多种分子机制来调节靶基因表达和途径功能，这可能使 Ey 在控制眼睛发育过程中的不同过程时具有更大的灵活性。
