锌指 MYND（髓样、神经和 DEAF-1）型含有 8 (ZMYND8) 是一种重要的表观遗传调节因子，在调控一系列重要细胞过程中发挥多方面的作用，包括增殖、凋亡、迁移、肿瘤抑制和分化。它通过协调神经元谱系定向基因的表达而成为神经元分化的关键参与者。本研究揭示了 ZMYND8 在调节 Sonic Hedgehog (SHH) 信号轴中的作用，这对于神经元分化至关重要。 ZMYND8 的基因缺失会导致全反式视黄酸 (ATRA) 诱导分化过程中 SHH 通路基因、GLI1 和 PTCH1 表达显着减少。研究发现 ZMYND8 和 RNA pol II S5P 共同占据 GLI1 和 PTCH1 基因启动子，在 ATRA 治疗后对其基因转录产生积极影响。有趣的是，ZMYND8被发现可以抵消Cyclopamine阻断上游SHH通路蛋白SMO的抑制作用，从而导致神经母细胞瘤细胞在用ATRA治疗后神经突形成增强。这些结果表明，ZMYND8 是 SHH 信号通路的表观遗传调节因子，在 ATRA 介导的神经母细胞瘤分化中具有巨大的治疗潜力。

Zinc Finger MYND (Myeloid, Nervy, and DEAF-1) type containing 8 (ZMYND8) is a crucial epigenetic regulator that plays a multifaceted role in governing a spectrum of vital cellular processes, encompassing proliferation, apoptosis, migration, tumor suppression, and differentiation. It has emerged as a key player in neuronal differentiation by orchestrating the expression of neuronal lineage-committed genes. The present study uncovers the role of ZMYND8 in regulating the Sonic Hedgehog (SHH) signaling axis, which is crucial for neuronal differentiation. Genetic deletion of ZMYND8 leads to a significant reduction in SHH pathway genes, GLI1, and PTCH1 expression during all-trans-retinoic acid (ATRA)-induced differentiation. ZMYND8 and RNA pol II S5P are found to co-occupy the GLI1 and PTCH1 gene promoters, positively impacting their gene transcription upon ATRA treatment. Interestingly, ZMYND8 is found to counteract the inhibitory effects of Cyclopamine that block the upstream SHH pathway protein SMO, resulting in enhanced neurite formation in neuroblastoma cells following their treatment with ATRA. These results indicate that ZMYND8 is an epigenetic regulator of the SHH signaling pathway and has tremendous therapeutic potential in ATRA-mediated differentiation of neuroblastoma.