Nuclear mobilities of cis-regulatory hubs in transcriptional control – HUBDYN

Eukaryotic genes are frequently controlled at a distance by cis-regulatory modules (CRMs) such as enhancers. Until very recently, it was assumed that CRMs formed close physical contacts with target genes to confer regulation, but this now been brought into doubt by new microscopy studies. The finding that both CRMs and transcription factors can coalesce into different hubs has raised new questions about the nuclear microenvironment required for transcriptional regulation, but beyond static images from microscopy in fixed cells, relatively little is known about their dynamics in 4D. We propose to combine a biophysical modeling framework within advanced live imaging techniques in both mouse and fly early developmental systems to interrogate the mobilities of transcriptional regulatory hubs, and how alterations in these properties and/or nuclear environment affect gene expression.