Regulatory encoding of quantitative variation in spatial activity of a Drosophila enhancer

Sci Adv. 2020 Dec 2;6(49):eabe2955. doi: 10.1126/sciadv.abe2955. Print 2020 Dec.

Abstract

Developmental enhancers control the expression of genes prefiguring morphological patterns. The activity of an enhancer varies among cells of a tissue, but collectively, expression levels in individual cells constitute a spatial pattern of gene expression. How the spatial and quantitative regulatory information is encoded in an enhancer sequence is elusive. To link spatial pattern and activity levels of an enhancer, we used systematic mutations of the yellow spot enhancer, active in developing Drosophila wings, and tested their effect in a reporter assay. Moreover, we developed an analytic framework based on the comprehensive quantification of spatial reporter activity. We show that the quantitative enhancer activity results from densely packed regulatory information along the sequence, and that a complex interplay between activators and multiple tiers of repressors carves the spatial pattern. Our results shed light on how an enhancer reads and integrates trans-regulatory landscape information to encode a spatial quantitative pattern.

Publication types

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

MeSH terms

  • Animals
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila* / genetics
  • Drosophila* / metabolism
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Developmental
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Wings, Animal / metabolism

Substances

  • Drosophila Proteins
  • Transcription Factors