Shared cis-regulatory modules control expression of the tandem paralogs midline and H15 in the follicular epithelium

Abstract

The posterior end of the follicular epithelium is patterned by midline (MID) and its paralog H15, the Drosophila homologs of the mammalian Tbx-20 transcription factor. We previously identified two cis-regulatory modules (CRMs) that recapitulate the endogenous pattern of mid in the follicular epithelium. Here, through CRISPR/Cas9 genome editing, we demonstrate redundant activity of these mid CRMs. While the deletion of either CRM alone generated marginal change in mid expression, the deletion of both CRMs reduced expression by 60%. Unexpectedly, the deletion of the 5’ proximal CRM of mid eliminated H15 expression. Interestingly, expression of these paralogs in other tissues remained unaffected in the CRMs deletion backgrounds. These results suggest that the paralogs are regulated by a shared-CRM that coordinates gene expression during posterior fate determination. The consistent overlapping expression of mid and H15 in various tissues may indicate that the paralogs could also be under shared regulation by other CRMs in these tissues.