We find the rate of cohesin loop extrusion in cells is set by NIPBL dosage and tunes many aspects of chromosome folding.
This provides a molecular basis for NIPBL haploinsufficiency in humans. 🧵👇
www.biorxiv.org/content/10.1...
-PDS5 facilitates NIPBL dissociation from cohesin by invading NIPBL binding site
-PDS5 strengthns CTCF boundaries by limiting NIPBL-cohesin life
-PDS5 lowers avg extrusion speed/depletion ups processivity
-Compartmentalization governed by competition of extrusion &polymer relaxation dynamics
-PDS5 facilitates NIPBL dissociation from cohesin by invading NIPBL binding site
-PDS5 strengthns CTCF boundaries by limiting NIPBL-cohesin life
-PDS5 lowers avg extrusion speed/depletion ups processivity
-Compartmentalization governed by competition of extrusion &polymer relaxation dynamics
Hi-C in cells depleted of PDS5 & now partially of NIPBL recover some of CTCF boundaries (+ also compartments)
Hi-C in cells depleted of PDS5 & now partially of NIPBL recover some of CTCF boundaries (+ also compartments)
PDS5+NIPBL could colocalize on cohesin leading to NIPBL unbinding! Loops often released but sometimes shrunk & NIPBL returned.
So PDS5 slows loop growth + speeds NIPBL unbinding by facilitated dissociation!
PDS5+NIPBL could colocalize on cohesin leading to NIPBL unbinding! Loops often released but sometimes shrunk & NIPBL returned.
So PDS5 slows loop growth + speeds NIPBL unbinding by facilitated dissociation!