Extended Data Fig. 9: TLs do not cause insulation at different length scales.

Insulation assesses Hi-C contacts spanning across a given locus up to a maximal distance w (top right insert). Contacts in a square window of size w were aggregated and the square was slid along the Hi-C diagonal. The score was normalized by its genome wide mean. Profiles show log2 of the score, such that a locus with profile value -1 has a two-fold reduced number of contacts spanning the locus up to distance w compared to the genome wide mean. Insulation scores are computed with the cooltools package (https://github.com/mirnylab/cooltools). We computed insulation profiles for Hi-C maps with a bin size of 128 kb for various window sizes from 256 kb up to ≈16 Mb. For every analyzed gene, the left and right columns show a 3 and 20 Mb Hi-C map with insulation profiles for different window sizes; the top and bottom panels show insulation profiles in expressing (on) and non-expressing (off) cells, respectively. The analysis shows little correlation between insulation and the formation of TLs: insulation profiles at the gene loci do not differ much between cell types with the gene on or off. For example, the Tg gene shows a moderate dip at scales up to ≈ 1 Mb in both thyroids (on) and myoblasts (off), and no dip in either cell type on the larger scale. Analysis of simulated TLs (Fig. 8 and Extended data Fig. 10) confirmed that TL formation does not cause large scale insulation (bottom row).