GSE22549
ChIP-seq Identification of Weakly Conserved Heart Enhancers
Accurate control of tissue-specific gene expression plays a pivotal role in heart development.  However, few cardiac transcriptional enhancers have thus far been identified. Extreme non-coding sequence conservation successfully predicts enhancers active in many tissues, but fails to identify substantial numbers of enhancers active in the heart.  We used ChIP-seq with the enhancer-associated protein p300 from mouse embryonic heart tissue to identify over three thousand candidate heart enhancers genome-wide.  In contrast to other studied tissues at this time-point, most candidate heart enhancers are not deeply conserved in vertebrate evolution.  Nevertheless, the testing of 130 candidate regions in a transgenic mouse assay revealed that most of them reproducibly function as enhancers active in the heart, irrespective of their degree of evolutionary constraint.  These results provide evidence for tissue-dependent differences in evolutionary constraint of enhancers acting through the transcriptional co-activator p300 at this time-point, and identify a large population of poorly conserved heart enhancers. Overall design: Examination of p300 binding in embryonic stage 11.5 mouse heart and midbrain