Functional analysis of a gene locus in response to non-canonical combinations of transcription factors

TL;DR

This study investigates how non-canonical combinations of transcription factors influence gene activity, revealing the gap gene network's capacity to correct expression deviations and maintaining precise gene activation patterns in Drosophila embryos.

Contribution

It provides new insights into the relationship between transcription factor levels and gene activation, highlighting the network's correction mechanisms and constraints on multi-enhancer loci.

Findings

Gene expression deviations still activate the eve locus.

eve stripes form at precise positions despite expression variability.

The gap gene network exhibits correction capacity.

Abstract

Transcription factor combinations determine gene locus activity and thereby cell identity. However, the precise link between concentrations of such activating transcription factors and target-gene activity is ambiguous. Here we investigate this link for the gap gene dependent activation of the even-skipped (eve) locus in the Drosophila embryo. We simultaneously measure the spatiotemporal gap gene concentrations in hemizygous and homozygous gap mutants, and link these to eve activity. Although changes in expression extend well beyond the genetically manipulated gene, nearly all expression alternations approximate the canonical combinations of activating levels in wild-type, sometimes necessitating pattern shifts. Expression levels that diverge from the wild-type repertoire still drive locus activation. Specific stripes in the homozygous mutants show partial penetrance, justifying their renown variable phenotypes. However, all eve stripes appear at highly reproducible positions, even though a broader span of gap gene expression levels activates eve. Our results suggest a correction capacity of the gap gene network and set constraints on the activity of multi-enhancer gene loci.