Validation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers.

ABSTRACT: We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs) using three computational prediction programs. Based on the predictions, 339 candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12 myoblasts for capacity to direct selective reporter gene expression to differentiated C2C12 myotubes. A subset of 19 CRMs validated as functional in the assay. The rate of predictive success reveals striking limitations of computational regulatory sequence analysis methods for CRM discovery. Motif-based methods performed no better than predictions based only on sequence conservation. Analysis of the properties of the functional sequences relative to inactive sequences identifies nucleotide sequence composition can be an important characteristic to incorporat

SUBMITTER: Kwon AT 

PROVIDER: S-EPMC3228787 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature