Validated negative regions (VNRs) in the VISTA database might be truncated forms of bona fide enhancers

Abstract

Abstract The VISTA enhancer database is a valuable resource for evaluating predicted regulatory sequences and studying various aspects of enhancers in mammalian genomes. In addition to thousands of validated positive regions (VPRs) in the human and mouse genomes, the database also contains similar numbers of validated negative regions (VNRs). We find that like the VPRs, the VNRs also are under strongly evolutionary constraints and are almost completely recalled by highly accurately predicted cis-regulatory modules (CRMs) in the genomes. However, both VNRs and VPRs are on average half as long as the recalling CRMs, while containing a small portion of non-enhancer sequences. These results suggest that both VNRs and VPRs might be truncated forms of long enhancers. It appears that VPRs might be at least partially functional in their truncated form under the assessed conditions, while VNRs might not be functional in their truncated forms and/or under the assessed conditions.