Open AccessHow affinity of the ELT-2 GATA factor binding to cis-acting regulatory sites controls C. elegans intestinal gene transcription
Author(s) -
Brett R. Lancaster,
James D. McGhee
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.190330
Subject(s) - biology , transcription factor , gene , caenorhabditis elegans , genetics , gata transcription factor , microbiology and biotechnology , gene expression , promoter
We define a quantitative relation between the affinity with which the intestine-specific GATA factor ELT-2 binds to cis acting regulatory motifs and the resulting transcription of asp-1, a target gene representative of genes involved in C. elegans intestine differentiation. By establishing an experimental system that allows unknown parameters (e.g., the influence of chromatin) to effectively cancel out, we show that levels of asp-1 transcripts increase monotonically with increasing binding affinity of ELT-2 to variant promoter TGATAA sites. The shape of the response curve reveals that the product of the unbound ELT-2 concentration in vivo (i.e. [ELT-2 free] or ELT-2 “activity”) and the largest ELT-XXTGATAAXX association constant (Kmax) lies in the range of 5-10. We suggest that this (unitless) product (K*max[ELT-2 free] or the equivalent product for any other transcription factor) provides an important quantitative descriptor of transcription-factor/regulatory-motif interaction in development, evolution and genetic disease. A more complicated model than simple binding affinity is necessary to explain the fact that ELT-2 appears to discriminate in vivo against equal-affinity binding sites that contain AGATAA instead of TGATAA.