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Dr. Cremins and colleagues at the University of Pennsylvania have designed a new class of 3D optogenetic tools for the directed, reversible rearrangement of 3D chromatin looping on short time scales using blue light. Enzymatically dead Cas9 and the CIBN protein from Arabidopsis thaliana heterodimerized with constitutively expressed CRY2 protein to bridge two genomic loci of interest by application of blue light. This process induces loop formation for the control of genome functions, including, but not limited to, gene expression, replication timing, and genome instability.
Light-activated dynamic looping (LADL) facilitates reversible and rapid loop synchronization for regulating gene expression with spatial and temporal control, without the need for an external chemical dimerizer. This method provides a gateway to understanding the role for 3D genome folding in regulating genome function in healthy human development and during the onset and progression of human disease.