|Di Huang|| at 11:00
Regulatory Pathways in Tissue-Specific Enhancers
Recent ChIP-seq experiments targeting the enhancer associated proteins p300 and CBP in embryonic and adult tissues produced genome-wide maps of tissue-specific enhancers. In this study, we explored the transcription factor binding site (TFBS) composition of tissue-specific enhancers and developed a computational model to map enhancers into regulatory pathways based on transcription factor (TF) interactions. By applying our model to heart enhancers, we identified 6 distinct heart regulatory pathways formed by 47 TFs. We observed spatial (ventricles, atria, and outflow tract) and developmental stage differences in regulatory activities of the identified pathways. Application of our method to two largely distinct types of heart enhancers – co-activated by key cardiac TFs and those recruiting p300 – allowed demonstrating that the main differences between these two sets reside in regulatory pathways and mechanisms in which they recruit. Similarly, we observed 6 forebrain and 5 limb regulatory pathways formed by SOX2, LRF, and AP4 (forebrain) and HOX family, DLX5, and CDX4 (limb) TFs. Our study and the developed model offer insight and provide novel tools for characterizing the regulatory pathways at the foundation of tissue-specific gene regulatory programs.