Exploring the role of eRNA in regulating gene expression.

Abstract

eRNAs as the products of enhancers can regulate gene expression via various possible ways, but which regulation way is more reasonable is debatable in biology, and in particular, how eRNAs impact gene expression remains unclear. Here we introduce a mechanistic model of gene expression to address these issues. This model considers three possible regulation ways of eRNA: Type-I by which eRNA regulates transcriptional activity by facilitating the formation of enhancer-promoter (E-P) loop, Type-II by which eRNA directly promotes the mRNA production rate, and mixed regulation (i.e., the combination of Type-I and Type-II). We show that with the increase of the E-P loop length, mRNA distribution can transition from unimodality to bimodality or vice versa in all the three regulation cases. However, in contrast to the other two regulations, Type-II regulation can lead to the highest mean mRNA level and the lowest mRNA noise, independent of the E-P loop length. These results would not only reveal the essential mechanism of how eRNA regulates gene expression, but also imply a new mechanism for phenotypic switching, namely the E-P loop can induce phenotypic switching.