A naturally occuring insertion of a single amino acid rewires transcriptional regulation by glucocorticoid receptor isoforms

Abstract

Significance For proteins to be able to have context-specific activities, they can adopt context-specific conformations that enhance or restrict their activity. For transcriptional regulatory factors, such a context-specific signal is provided by the sequence of the DNA response element to which it binds. Here we show how one signal, an alternative splicing event, rewires a transcriptional regulatory protein to respond differently to a second signal, the DNA sequence to which it binds, by changing the functional interplay between protein domains. Together, our findings argue that bidirectional allosteric signaling between the DNA:protein interface and other regulatory domains fine tunes the activity of transcriptional regulatory factors toward individual target genes.</jats:p