Multiple Epigenetic Factors Co-localize with HMGN Proteins in A-Compartment Chromatin

Nucleosomal binding proteins, HMGN, are a family of chromatin architectural proteins that are abundant in the mammalian cell nucleus. Although previous studies have discovered that HMGN proteins have important roles in gene regulation and chromatin accessibility, whether and how HMGN proteins affect higher-order chromatin status remains unknown. In this study we determined the roles that HMGN1 and HMGN2 proteins play in higher-order chromatin structures in three different cell types. We interrogated data generated in situ, using several techniques, including Hi-C, Promoter Capture Hi-C, ChIP-seq, and ChIP-MS. Our results show that HMGN proteins occupy the A compartment in the 3D nucleus space. In particular, HMGN proteins occupy genomic regions involved in cell-type-specific long-range promoter-enhancer interactions. Interestingly, depletion of HMGN proteins in three different cell types does not cause structural changes in higher-order chromatin, i.e., in topologically associated domains (TADs) and in A/B compartment scores.