Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
BMC Genomics. 2024 Jan 23;25(1):103. doi: 10.1186/s12864-024-10017-7.
The Ets domain transcription factors direct diverse biological processes throughout all metazoans and are implicated in development as well as in tumor initiation, progression and metastasis. The Drosophila Ets transcription factor Pointed (Pnt) is the downstream effector of the Epidermal growth factor receptor (Egfr) pathway and is required for cell cycle progression, specification, and differentiation of most cell types in the larval eye disc. Despite its critical role in development, very few targets of Pnt have been reported previously. Here, we employed an integrated approach by combining genome-wide single cell and bulk data to identify putative cell type-specific Pnt targets. First, we used chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) to determine the genome-wide occupancy of Pnt in late larval eye discs. We identified enriched regions that mapped to an average of 6,941 genes, the vast majority of which are novel putative Pnt targets. Next, we integrated ChIP-seq data with two other larval eye single cell genomics datasets (scRNA-seq and snATAC-seq) to reveal 157 putative cell type-specific Pnt targets that may help mediate unique cell type responses upon Egfr-induced differentiation. Finally, our integrated data also predicts cell type-specific functional enhancers that were not reported previously. Together, our study provides a greatly expanded list of putative cell type-specific Pnt targets in the eye and is a resource for future studies that will allow mechanistic insights into complex developmental processes regulated by Egfr signaling.
Ets 结构域转录因子在所有后生动物中指导着多样化的生物学过程，并且与发育以及肿瘤的起始、进展和转移有关。果蝇 Ets 转录因子 Pointed（Pnt）是表皮生长因子受体（Egfr）途径的下游效应因子，是幼虫眼盘大多数细胞类型的细胞周期进展、特化和分化所必需的。尽管它在发育中起着至关重要的作用，但之前报道的 Pnt 靶标很少。在这里，我们采用了一种综合方法，将全基因组单细胞和批量数据相结合，以鉴定潜在的细胞类型特异性 Pnt 靶标。首先，我们使用染色质免疫沉淀结合高通量测序（ChIP-seq）来确定 Pnt 在晚期幼虫眼盘中的全基因组占据情况。我们确定了富集区域，这些区域平均映射到 6941 个基因，其中绝大多数是新的潜在 Pnt 靶标。接下来，我们将 ChIP-seq 数据与另外两个幼虫眼单细胞基因组数据集（scRNA-seq 和 snATAC-seq）整合在一起，揭示了 157 个潜在的细胞类型特异性 Pnt 靶标，这些靶标可能有助于介导 Egfr 诱导分化时的独特细胞类型反应。最后，我们整合的数据还预测了以前未报道的细胞类型特异性功能增强子。总之，我们的研究提供了一个大大扩展的眼组织中潜在的细胞类型特异性 Pnt 靶标的列表，并且是未来研究的资源，这些研究将使我们能够深入了解 Egfr 信号调节的复杂发育过程的机制。
