Recently, de novo mutations of transcription factor 20 (TCF 20) were found in patients with autism by large‐scale exome sequencing. However, how TCF 20 modulates brain development and whether its dysfunction causes ASD remain unclear. Here, we show that TCF 20 deficits impair neurogenesis in mouse. TCF 20 deletion significantly reduces the number of neurons, which leads to abnormal brain functions. Furthermore, transcriptome analysis and ChIP ‐qPCR reveal that the DNA demethylation factor TDG is a downstream target gene of TCF 20. As a nonspecific DNA demethylation factor, TDG potentially affects many genes. Combined TDG ChIP ‐seq and GO analysis of TCF 20 RNA ‐Seq identifies T‐cell factor 4 (TCF ‐4) as a common target. TDG controls the DNA methylation level in the promoter area of TCF ‐4, affecting TCF ‐4 expression and modulating neural differentiation. Overexpression of TDG or TCF ‐4 rescues the deficient neurogenesis of TCF 20 knockdown brains. Together, our data reveal that TCF 20 is essential for neurogenesis and we suggest that defects in neurogenesis caused by TCF 20 loss are associated with ASD .

中文翻译：

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TCF20 功能障碍导致小鼠皮质神经发生缺陷和自闭症样行为。

最近，从头通过大规模外显子组测序在自闭症患者中发现转录因子 20 (TCF 20) 的突变。然而，TCF 20 如何调节大脑发育以及其功能障碍是否导致 ASD 仍不清楚。在这里，我们表明 TCF 20 缺陷会损害小鼠的神经发生。TCF 20 缺失显着减少了神经元的数量，从而导致脑功能异常。此外，转录组分析和 ChIP-qPCR 表明 DNA 去甲基化因子 TDG 是 TCF 20 的下游靶基因。作为非特异性 DNA 去甲基化因子，TDG 可能影响许多基因。TDG ChIP-seq 和 TCF 20 RNA-Seq 的 GO 分析将 T 细胞因子 4 (TCF-4) 确定为共同目标。TDG控制TCF-4启动子区域的DNA甲基化水平，影响TCF-4表达并调节神经分化。TDG 或 TCF-4 的过表达挽救了 TCF 20 敲低大脑的神经发生缺陷。总之，我们的数据表明 TCF 20 对神经发生至关重要，我们认为由 TCF 20 损失引起的神经发生缺陷与 ASD 相关。