Concentration-dependent transcriptional switching through a collective action of cis-elements.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35947668.
- Also identified by DOI 10.1126/sciadv.abo6157 and PMC identifier 9365274.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Gene expression specificity of homeobox transcription factors has remained paradoxical. WUSCHEL activates and represses <i>CLAVATA3</i> transcription at lower and higher concentrations, respectively. We use computational modeling and experimental analysis to investigate the properties of the cis-regulatory module. We find that intrinsically each cis-element can only activate <i>CLAVATA3</i> at a higher WUSCHEL concentration. However, together, they repress <i>CLAVATA3</i> at higher WUSCHEL and activate only at lower WUSCHEL, showing that the concentration-dependent interactions among cis-elements regulate both activation and repression. Biochemical experiments show that two adjacent functional cis-elements bind WUSCHEL with higher affinity and dimerize at relatively lower levels. Moreover, increasing the distance between cis-elements prolongs WUSCHEL monomer binding window, resulting in higher <i>CLAVATA3</i> activation. Our work showing a constellation of optimally spaced cis-elements of defined affinities determining activation and repression thresholds in regulating <i>CLAVATA3</i> transcription provides a previously unknown mechanism of cofactor-independent regulation of transcription factor binding in mediating gene expression specificity.