Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases. (August 2019)

• Record Type: Journal Article
• Authors: Wei, Chia-Lin; Nicolis, Silvia K; Zhu, Yanfen; Pagin, Miriam
• Is Part Of: Journal of experimental neuroscience. Volume 13(2019)
• Publication Date: 2019-08
• Subjects: Sox2 -- neural stem cells -- enhancers -- neurodevelopmental disease -- long-range interactions; Neurosciences -- Periodicals; Nervous system -- Periodicals; Nervous System Diseases; Neurosciences; Nervous system; Neurosciences; Periodicals; Electronic journals; Periodicals; 573.8
• DOI: 10.1177/1179069519868224
• Languages: English
• ISSNs: 1179-0695

Abstract

In our article, we asked whether Sox2, a transcription factor important in brain development and disease, is involved in gene regulation through its action on long-range interactions between promoters and distant enhancers. Our findings highlight that Sox2 shapes a genome-wide network of promoter-enhancer interactions, acting by direct binding to these elements. Sox2 loss affects the three-dimensional (3D) genome and decreases the activity of a subset of genes involved in Sox2-bound interactions. At least one of such downregulated genes, Socs3, is critical for long-term neural stem cell maintenance. These results point to the possibility of identifying a transcriptional network downstream to Sox2, and involved in neural stem cell maintenance. In addition, interacting Sox2-bound enhancers are often connected to genes which are relevant, in man, to neurodevelopmental disease; this may facilitate the detection of functionally relevant mutations in regulatory elements in man, contributing to neural disease.