RT Journal Article
SR Electronic
T1 COMPASS Family Histone Methyltransferase ASH2L Mediates Corticogenesis via Transcriptional Regulation of Wnt Signalling
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 413674
DO 10.1101/413674
A1 Liang Li
A1 Xiangbin Ruan
A1 Chang Wen
A1 Pan Chen
A1 Wei Liu
A1 Liyuan Zhu
A1 Pan Xiang
A1 Xiaoling Zhang
A1 Qunfang Wei
A1 Lin Hou
A1 Bin Yin
A1 Jiangang Yuan
A1 Boqin Qiang
A1 Pengcheng Shu
A1 Xiaozhong Peng
YR 2018
UL http://biorxiv.org/content/early/2018/09/10/413674.abstract
AB Cell fate specification in neural progenitor cells (NPCs) is orchestrated via extrinsic and intrinsic molecular programs, and histone methylation in these decisions has been ascribed to a crucial function regulating gene expression. Here, 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 signalling, disrupting their transcription and consequently inhibiting the proliferation ability of NPCs in late stages of neurogenesis. Consistently, Ash2l conditional mutants exhibit thinning neocortex with reduced upper layer neurons and altered neuronal position. Moreover, overexpressing β-catenin after Ash2l elimination or knockdown can rescue the proliferation deficiency of NPCs both in vivo and in vitro. These results demonstrate an essential and highly specific role for Ash2l in controlling NPCs proliferation and late-born neurons lamination in corticogenesis via transcriptionally regulating Wnt-β-catenin signalling, and provide clues to how the COMPASS family epigenetic factors coordinate cell fate determination during cortex development.