COMPASS Family Histone Methyltransferase ASH2L Mediates Corticogenesis via Transcriptional Regulation of Wnt Signaling [RNA-Seq 2]

We show that the COMPASS family histone methyltransferase co-factor ASH2L is required in NPCs proliferation and upper layer cortical projection neurons production and position. Deletion of ASH2L impairs trimethylation of H3K4 and transcriptional machinery specifically for subsets of Wnt-β-catenin signaling, disrupting their transcription and consequently inhibiting the proliferation ability of NPCs in late stages of neurogenesis. We generated D6-Cre Ash2l conditional knockout mice.Through RNA-seq and ChIPseq of dorsal cortex from Ash2l WT and cKO mice to identify the role of Ash2l during corticogenesis

我们的研究证实，COMPASS复合物家族（COMPASS family）的组蛋白甲基转移酶辅因子ASH2L，在神经前体细胞（Neural Progenitor Cells, NPCs）的增殖以及皮层上层投射神经元的产生与定位中具有必需作用。ASH2L的缺失会损伤H3K4三甲基化修饰以及Wnt-β-连环蛋白（Wnt-β-catenin）信号通路特定亚群的转录调控机制，扰乱其转录过程，进而在神经发生后期抑制神经前体细胞的增殖能力。本研究构建了D6-Cre介导的Ash2l条件性敲除（conditional knockout, cKO）小鼠模型，并通过对Ash2l野生型（Wild Type, WT）和条件性敲除小鼠的背侧皮层开展RNA测序（RNA-seq）与染色质免疫沉淀测序（ChIP-seq），以解析Ash2l在皮层发生过程中的具体功能。