Histone H3K27ac spreads from enriched chromatin domains into neighboring regions upon loss of CTCF binding.
Acetylation of histone H3 at lysine 27 (H3K27ac) is enriched at enhancers and highly transcribed genes. Our previous study showed that an H3K27ac-enriched chromatin domain expanded into neighboring regions following the deletion of CTCF-binding motifs flanking the domain. In this study, we explored the spreading of H3K27ac on a genome-wide scale by analyzing its distribution around CTCF-binding sites in human K562 cells and examining changes upon CTCF loss. We found that a subset of CTCF-binding sites demarcates H3K27ac-enriched domains. Upon loss of CTCF binding, H3K27ac levels increased in most regions adjacent to these domains, indicating that H3K27ac can spread into neighboring chromatin. This spreading was accompanied by elevated transcription of nearby genes. Chromatin features, including histone modifications, CTCF-binding intensity, and CTCF-mediated chromatin interactions, were associated with the H3K27ac spreading. Notably, enhancers were more enriched within domains that exhibited H3K27ac spreading compared to those that did not, and the deletion of enhancers from the CTCF motif-deficient β-globin locus attenuated the spreading. These findings indicate that CTCF-binding sites serve as boundaries for H3K27ac-enriched domains and that, in the absence of CTCF binding, H3K27ac can spread into neighboring regions. H3K27ac spreading appears to be influenced by multiple chromatin features and to contribute to the transcriptional increase of nearby genes.