THAP1 is cell type dependent regulator of SP1 family crucial for dystonic syndromes in human and rat [SHSY5Y_ChIP-seq]

THAP1 is a transcription factor and its mutations are responsible for DYT6 dystonia. However, how THAP1 mutations lead to these gene expression alterations and whether the gene expression changes are also reflected in the brain of THAP1 patients are still unclear. In this study we used epigenetic and transcriptomic approaches combined with multiple model systems to uncover the function of THAP1 and the potential pathogenesis of DYT6 dystonia. THAP1 mutations lead to dysregulation of genes mainly through regulation of SP1 family members, SP1 and SP4, in a cell type dependent manner. Overall design: ChIP-seq analysis of wild-type and THAP1 heterozygous knock-out SHSY5Y cells

THAP1是一种转录因子，其突变可引发DYT6肌张力障碍。然而，THAP1突变如何导致此类基因表达异常，以及此类基因表达改变是否也会在THAP1患者的脑组织中有所体现，目前仍不明确。本研究联合表观遗传学与转录组学研究方法及多种模型系统，旨在阐明THAP1的功能与DYT6肌张力障碍的潜在发病机制。THAP1突变主要通过以细胞类型依赖性方式调控SP1家族成员（SP1与SP4），引发基因表达失调。整体实验设计：对野生型及THAP1杂合敲除的SH-SY5Y细胞开展染色质免疫共沉淀测序（ChIP-seq）分析。