While our chromatin state analysis focused at the nucleosome resolution (200-bp), we also studied the overall co-occurrence of chromatin states across tissues at a larger 2Mb resolution to recognize higher-order properties (Fig. 5d). This analysis revealed that 2Mb segments rich in active enhancers are constrained to approximately 40% of the genome (clusters c1-c6), with the remainder marked predominantly by inactive regions (c7-c11), consistent with the identification of two large chromatin conformation compartments12,61. However, both compartments can be further subdivided by their chromatin state composition: inactive regions separate into predominantly quiescent (40%; c9, c11), heterochromatic (10%, c10), or bivalent (10%, c7-c8) marked regions; and active regions separate into regions rich in multiple marks (c3 and c6, showing a large diversity of active, ReprPC, and bivalent states), weakly-transcribed regions (c5, showing primarily Enh and TxWk states), and regions of intermediate activity (c1, c2, c4). As these subdivisions are based on average state density across a large diversity of cell types, we expected them to be stable chromosomal features, and indeed, they showed strong differences in gene density, CpG island occupancy, lamina association62-63 and cytogenetic bands (Fig. 5d, Extended Data 5d).
