Genomic Ultraconserved Elements Show Exceptional Association with Polycomb Proteins and Positioned Nucleosomes

Ultraconserved elements (UCEs) are genomic sequences exhibiting exceptional evolutionary conservation, yet their biological functions remain poorly understood. Here, we investigated protein associations with 12,813 human UCEs using large collections of publicly available ChIP-seq data. Analysis of ChIP-Atlas revealed that Polycomb-group proteins showed the strongest association with UCEs among the protein families examined. Particularly striking enrichments were observed for PHC1 (223-fold), CBX7 (130-fold), EPOP (86-fold), and PCGF2 (57-fold). Complementary analysis using the ReMap database confirmed strong UCE enrichment for PHC1, CBX7, and PCGF2, with PHC1 again showing the strongest association (212-fold). Remarkably, 43% of non-redundant PHC1 ReMap peaks overlapped UCEs. We further examined UCE positions relative to nucleosomes using NucleoATAC-defined dyads in GM12878 cells. Natural UCEs occurred significantly closer to positioned nucleosomes than expected from 1000 randomized UCE datasets, with the strongest enrichment observed within 250 bp of nucleosome dyads (2.84-fold; empirical p ≈ 0.001). Together, these observations reveal a strong association of UCEs with Polycomb proteins and positioned nucleosomes, suggesting that ultraconserved DNA occurs within a distinctive chromatin environment potentially related to its unusual sequence and structural properties.