GSE204690
Cell type specific ATACseq (Crosslinked and TF-Sorted ATAC-seq (CaTS-ATAC)) reveals two distinct cis regulatory strategies for Shh interpretation in the mouse ventral neural tube
In many developing tissues the spatial and temporal pattern of gene expression is organised by secreted signals functioning in a graded manner over multiple cell diameters. Cis Regulatory Elements (CREs) interpret these graded inputs to control gene expression. How this is accomplished remains poorly understood. The morphogen Sonic hedgehog (Shh) acts in a graded manner to direct neural progenitor specification in the neural tube. Here, we uncover two distinct ways in which CREs translate graded Shh signaling into differential gene expression. A common set of CREs are used to control gene activity in the majority of ventral neural progenitors. These CREs integrate cell type specific inputs to control gene expression. By contrast, the most ventral progenitors use a unique set of CREs. These are established by the pioneer factor FOXA2, paralleling the role of FOXA2 in endoderm. Moreover, FOXA2 binds a subset of the same sites in neural and endoderm cells. Together the data identify distinct cis regulatory strategies for the interpretation of morphogen signaling and raise the possibility of an evolutionarily conserved role for Foxa2-mediated cell specification across tissues. Overall design: CaTS-ATAC timecourse of a cellular model of spinal cord differentiation covering specification of four neural progenitor cell types. Biological triplicates (independent differentiations)