THAP1 is a master regulator of zinc finger transcription factors guiding gastrulation of murine embryos [ChIP-seq_SH]

Gastrulation and early organogenesis are remarkable processes of early embryonic development. Our previous study showed that deletion of DYT6 gene product THAP1 leads to embryonic lethality at the stage of gastrulation and early organogenesis. However, the function of THAP1 in regulating gene expression, as well as its role in regulating embryo gastrulation and early organogenesis are not well characterized. In this study, we used different in vitro and in vivo models to characterize the function of THAP1 in regulating gene expression and in controlling embryonic development, which could help us to understand pathogenesis of THAP1-associated disorders and provide data to characterize the transcription regulation of gastrulation of murine embryo. THAP1 and CSNK2A1 knock-out SH-SY5Y cells were generated and CTCF and YY1 ChIP-seq were performed to analyze their genomic bindings

原肠胚形成（gastrulation）与早期器官发生（early organogenesis）是早期胚胎发育中的核心进程。本课题组此前的研究表明，DYT6基因的编码产物THAP1的敲除会引发胚胎在原肠胚形成与早期器官发生阶段死亡。然而，THAP1在调控基因表达方面的功能，以及其在胚胎原肠胚形成与早期器官发生过程中的作用，目前尚未得到充分阐释。在本研究中，我们借助多种体外（in vitro）与体内（in vivo）模型，对THAP1调控基因表达以及控制胚胎发育的功能进行了系统解析。本研究有助于阐明THAP1相关疾病的发病机制，并可为解析小鼠胚胎原肠胚形成过程中的转录调控机制提供数据支持。我们构建了THAP1与CSNK2A1双敲除的SH-SY5Y细胞系，并开展了CTCF与YY1的染色质免疫共沉淀测序（ChIP-seq）实验，以分析二者的基因组结合特征。