Extended Data Figure 1: Description of allele-specific Hi-C and ATAC–seq.

a, Schematic of hybrid mouse strains used for all experiments. b, Top, scheme outlining differentiation of ES cells to NPCs and picking of clones. Bottom, scheme outlining CRISPR deletion of the mega-domain boundary in ES cells, differentiation to NPCs and the picking of clones. c, Schematic of Hi-C library generation. d, Schematic of the Hi-C alignment strategy. Paired-end reads are aligned to a ‘diploid’ genome consisting of 22 chromosomes from Cast, and 22 chromosomes from 129 (1–19 X, Y, M). The interaction row shows all possible paired-end read combinations between the 129, Cast and ambiguous (AMB) genomes. e, Schematic showing the re-assignment of a subset of ‘cis’ interactions. Paired-end reads in which one side uniquely aligned to an allele and the other side aligned equally to both alleles (AMB), were re-classified as allelic reads, only if both reads aligned to the same chromosome (cis). f, Cartoon explaining the re-assignment of 129:amb or cast:amb cis interactions. g, Scheme for ATAC–seq library preparation. Cells are lysed followed by incubation with adaptor-loaded hyperactive Tn5 transposase. The transposase integrates into accessible DNA, and these fragments are then directly amplified and sequenced. h, Scheme for allele-specific ATAC–seq data analysis. i, SNP-mapping simulation. For each SNP location on the X chromosome, all overlapping 50 bp reads were extracted (50 total) for each of the 129 and Cast alleles. All reads were then processed through the Hi-C and ATAC–seq mapping pipelines described in the Methods to measure assignment accuracy. Results are shown in the table.