| Literature DB >> 33544864 |
Yanxin Xu1, Jiajie Xi1, Guiying Wang1, Zhenming Guo2,3, Qiaoyi Sun1, Chenqi Lu4, Li Ma1, Yukang Wu1, Wenwen Jia1, Songcheng Zhu1, Xudong Guo1, Shan Bian2, Jiuhong Kang1.
Abstract
Long noncoding RNAs (lncRNAs) play a wide range of roles in the epigenetic regulation of crucial biological processes, but the functions of lncRNAs in cortical development are poorly understood. Using human embryonic stem cell (hESC)-based 2D neural differentiation approach and 3D cerebral organoid system, we identified that the lncRNA PAUPAR, which is adjacent to PAX6, plays essential roles in cortical differentiation by interacting with PAX6 to regulate the expression of a large number of neural genes. Mechanistic studies showed that PAUPAR confers PAX6 proper binding sites on the target neural genes by directly binding the genomic regions of these genes. Moreover, PAX6 recruits the histone methyltransferase NSD1 through its C-terminal PST enrichment domain, then regulate H3K36 methylation and the expression of target genes. Collectively, our data reveal that the PAUPAR/PAX6/NSD1 complex plays a critical role in the epigenetic regulation of hESC cortical differentiation and highlight the importance of PAUPAR as an intrinsic regulator of cortical differentiation.Entities:
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Year: 2021 PMID： 33544864 PMCID： PMC7913681 DOI： 10.1093/nar/gkab030
Source DB: PubMed Journal: Nucleic Acids Res ISSN： 0305-1048 Impact factor: 16.971