Work by Zhongming Li, Amir Rattner, Yanshu Wang, Phil Smallwood, and Mark Sabbagh from the Nathans lab:

Central nervous system (CNS) vascular endothelial cells exhibit a distinctive gene expression program that is foundational for the blood-brain barrier (BBB).  Previous research identified candidate cis-regulatory elements (enhancers and repressors) that were hypothesized to control this program.  Using transgenic mice and recombinant adeno-associated virus vectors (rAAVs), Zhongming Li and his colleagues on the Nathans laboratory have interrogated these candidate cis-regulatory elements in vivo.  These experiments show that an 850 bp genomic DNA segment ~60 kb 5’ of Slc2a1, a gene that encodes an essential BBB transporter protein, possesses enhancer activity that is (1) specific for CNS endothelial cells and (2) both necessary and sufficient for BBB+ endothelial cells gene expression.  A screen of >8,000 genomic DNA segments that represent candidate CNS endothelial cell-specific cis-regulatory elements revealed several hundred with enhancer activity.  Transcription factors ERG and LEF1, the partner of beta-catenin, were shown to occupy sites in brain EC chromatin that are highly enriched in candidate and experimentally validated cis-regulatory elements, lending strong support to a model in which canonical Wnt signaling activates the BBB program via LEF1.