RT Journal Article SR Electronic T1 Enhancer-promoter association determines Sox2 transcription regulation in mouse pluripotent cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 590745 DO 10.1101/590745 A1 Lei Huang A1 Qing Li A1 Qitong Huang A1 Siyuan Kong A1 Xiusheng Zhu A1 Yanling Peng A1 Yubo Zhang YR 2019 UL http://biorxiv.org/content/early/2019/03/28/590745.abstract AB Distal enhancer-promoter associations are essential for transcription control and emerging as a common epigenetic way to determine gene expression in eukaryotes. However, it remains as an uncultivated land on how their diversity influences gene transcription during development. In this study, we select three defined Sox2 associated enhancers (E1, E2 and E3), representing different distal interaction categories, to further explore their biological effects. We construct three enhancer-knockout cells via CRISPR/Cas9 system in mouse embryonic stem cells. Results show that these associations carry out various biological features. Embryonic stem cell specific association (E1) speeds up cell cycle and involves in cardiac development, which has been validated in vivo. In contrast, the indirect one (E2) restrains nerve differentiation and has potential effect on lipid metabolism. The common one (E3) promotes nerve differentiation and inhibits oxidation-reduction process. Together, these different associations determine Sox2 transcription and function specificity in mouse embryonic stem cells. Our study will enable a way for exploring miscellaneous spatiotemporal gene transcription control and advancing quantitative knowledge by utilizing three-dimensional genomic information.Summary statement Sox2 transcription is complicated in mouse embryonic stem cells. It involves in heavily enhancer-promoter associations, which might make it a suitable model for phase-separation study. To decompose this cooperative regulation, diverse interactions are investigated. The biological effects have been explored in multiple perspectives. This may represent a quantitative way to explore and a potential new strategy to transcription control study.