Nr2f1 enhancers have distinct functions in controlling Nr2f1 expression during cortical development

• 成果类型: Article
• 署名作者: Liu, Zhidong; Ypsilanti, Athena R.; Papadimitriou, Eirene Markenscoff-; Dickel, Diane E.; Sanders, Stephan J.; Dong, Shan; Pennacchio, Len A.; Visel, Axel; Rubenstein, John L.
• 署名单位: University of California System; University of California San Francisco; Cornell University; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of Oxford; University of California System; University of California San Francisco; United States Department of Energy (DOE); Joint Genome Institute - JGI; University of California System; University of California Berkeley; University of California System; University of California Merced
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10645
• DOI: 10.1073/pnas.2402368121
• 发表日期: 2024-10-01
• 关键词: emx2 expression; RESOLUTION; chromatin; coup-tf1; IDENTITY; cortex; atlas; wnt

摘要

There is evidence that transcription factor (TF) encoding genes, which temporally control development in multiple cell types, can have tens of enhancers that regulate their expression. The NR2F1 TF developmentally promotes caudal and ventral cortical regional fates. Here, we epigenomically compared the activity of Nr2f1's enhancers during mouse cortical development with their activity in a transgenic assay. We identified at least six that are likely to be important in prenatal cortical development, with three harboring de novo mutants identified in ASD individuals. We chose to study the function of two of the most robust enhancers by deleting them singly or together. We found that they have distinct and overlapping functions in driving Nr2f1's regional and laminar expression in the developing cortex. Thus, these two enhancers, probably in combination with the others that we defined epigenetically, precisely tune Nr2f1's regional, cell type, and temporal expression during corticogenesis.