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

Development. 2022 Nov 15;149(22):dev201016. doi: 10.1242/dev.201016. Epub 2022 Nov 16.

Abstract

The posterior end of the follicular epithelium is patterned by midline (MID) and its paralog H15, the Drosophila homologs of the mammalian Tbx20 transcription factor. We have previously identified two cis-regulatory modules (CRMs) that recapitulate the endogenous pattern of mid in the follicular epithelium. Here, using CRISPR/Cas9 genome editing, we demonstrate redundant activity of these mid CRMs. Although 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 CRM 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.

Keywords: Cis-regulation; Anterior-posterior axis coordination; Developmental genes; Gene regulatory network; Genes tagging; Shared enhancers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Epithelium / metabolism
  • Gene Expression Regulation, Developmental*
  • Mammals / genetics
  • T-Box Domain Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Drosophila Proteins
  • Transcription Factors
  • H15 protein, Drosophila
  • T-Box Domain Proteins