Extensive Chromatin Structure-Function Associations Revealed by Accurate 3D Compartmentalization Characterization

A/B compartments are observed in Hi-C data and coincide with eu/hetero-chromatin. However, many genomic regions are ambiguous under A/B compartment scheme. We develop MOSAIC (MOdularity and Singular vAlue decomposition-based Identification of Compartments), an accurate compartmental state detection scheme. MOSAIC reveals that those ambiguous regions segregate into two additional compartmental states, which typically correspond to short genomic regions flanked by long canonical A/B compartments with opposite activities. They are denoted as micro-compartments accordingly. In contrast to the canonical A/B compartments, micro-compartments cover similar to 30% of the genome and are highly dynamic across cell types. More importantly, distinguishing the micro-compartments underpins accurate characterization of chromatin structure-function relationship. By applying MOSAIC to GM12878 and K562 cells, we identify CD86, ILDR1 and GATA2 which show concordance between gene expression and compartmental states beyond the scheme of A/B compartments. Taken together, MOSAIC uncovers fine-scale and dynamic compartmental states underlying transcriptional regulation and disease.