A collaborative study by the UTokyo-KI LINK program, headed by Camilla Björkegren from Karolinska Institutet, Kristian Jeppsson and Katsuhiko Shirahige from The University of Tokyo shows that a protein complex named Smc5/6 binds DNA structures called positive supercoils. These form when the chromosomal DNA double helix folds onto itself due to overtwisting caused by transcription, which is the first step in gene expression.
The study presents in vivo data indicating that Smc5/6 binds to the base of chromosome loops in regions that contain high levels of transcription-induced positive supercoils. The complex is also shown to control the three-dimensional (3D) organization of these regions.
Computational machine learning provides additional results supporting that transcription-induced positive supercoils determine the chromosomal binding pattern of Smc5/6. Finally, in vitro single molecule analysis, performed by the team of Dr. Eugene Kim at Max Planck Institute in Frankfurt, provides direct evidence that Smc5/6 preferentially binds positive DNA supercoils.
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