THAP1 is cell type dependent regulator of SP1 family crucial for dystonic syndromes in human and rat [Striatum_RNA-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.THAP1是一种转录因子（transcription factor），其突变可导致DYT6型肌张力障碍（DYT6 dystonia）。然而，THAP1突变如何引发此类基因表达改变，以及此类基因表达变化是否也能在THAP1患者的脑组织中得到体现，目前仍不明确。本研究联合运用表观遗传学（epigenetics）与转录组学（transcriptomics）研究手段，并结合多种模型体系，旨在阐明THAP1的功能及DYT6型肌张力障碍的潜在发病机制。本研究发现，THAP1突变主要通过细胞依赖性地调控SP1家族成员SP1及SP4，进而引发基因表达失调。