Disrupting the three-dimensional regulatory topology of the Pitx1 locus results in overtly normal development.

ABSTRACT: Developmental gene expression patterns are orchestrated by thousands of distant-acting transcriptional enhancers. However, identifying enhancers essential for the expression of their target genes has proven challenging. Maps of long-range regulatory interactions may provide the means to identify enhancers crucial for developmental gene expression. To investigate this hypothesis, we used circular chromosome conformation capture coupled with interaction maps in the mouse limb to characterize the regulatory topology of Pitx1, which is essential for hindlimb development. We identified a robust hindlimb-specific interaction between Pitx1 and a putative hindlimb-specific enhancer. To interrogate the role of this interaction in Pitx1 regulation, we used genome editing to dele

SUBMITTER: Sarro R 

PROVIDER: S-EPMC5963865 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature