基因表达调控的特定时空域非常关键于胚胎发育。近期研究发现 GLTSCR1 是癌症研究中基因转录延长调控因子，但对于 GLTSCR1 的功能，特别是在胚胎发育方面，了解尚不足够。我们发现 GLTSCR1 损失会导致小鼠胚胎致死，而同时还具有严重天生心脏缺陷（CHDs）。在神经嵴细胞中，针对 Gltscr1 的条件性删除也会导致心室隔缺损和右室双出口，最终导致小鼠新生儿的死亡。在机制上，GLTSCR1 的缺失促进了 NPPA 基因的表达，同时协同了 NPPA 增强子中和 CHD 相关的 G 等位基因 rs56153133，释放 NPPA 启动子上的转录因子 ZNF740 的结合位点。这些研究结果表明 GLTSCR1 是一种候选的 CHD 相关基因。© 2023. The Author(s).

Precise and specific spatiotemporal domains of gene expression regulation are critical for embryonic development. Recent studies have identified GLTSCR1 as a gene transcriptional elongation regulator in cancer research. However, the function of GLTSCR1, especially in embryonic development, remains poorly understood. Here, we found that GLTSCR1 was essential for cardiac development because Gltscr1 knockout (Gltscr1-/-) led to embryonic lethality in mice with severe congenital heart defects (CHDs). Ventricular septal defect and double outflow right ventricular were also observed in neural crest cells with conditional deletion of Gltscr1, which were associated with neonatal lethality in mice. Mechanistically, GLTSCR1 deletion promoted NPPA expression by coordinating the CHD risk G allele of rs56153133 in the NPPA enhancer and releasing the transcription factor ZNF740-binding site on the NPPA promoter. These findings demonstrated that GLTSCR1 acts as a candidate CHD-related gene.© 2023. The Author(s).