Topologically Associating Domains regulate gene activity by restricting enhancer-promoter loops. TADs are formed by loop extrusion and its blocking by CTCF at their boundaries. How optimal separation between TADs is achieved remains incompletely understood.
I will present our recent work showing that most TAD boundaries consist of clustered CTCF sites, with each site imperfectly and additively contributing to loop extrusion blocking. Moreover, I will present unpublished biophysical modeling and data intersection studies that reveals how extended boundaries directly reduce spurious inter-TAD intermingling as well.
