Integrated epigenomic analysis stratifies chromatin remodellers into distinct functional groups

Background: ATP-dependent chromatin remodelling complexes are responsible for establishing and maintaining the positions of nucleosomes. Chromatin remodellers are targeted to chromatin by transcription factors and noncoding RNA to remodel the chromatin into functional states. However, the infuence of chromatin remodelling on shaping the functional epigenome is not well understood. Moreover, chromatin remodellers have not been exten‑ sively explored as a collective group across two-dimensional and three-dimensional epigenomic layers.

Results: Here, we have integrated the genome-wide binding profles of eight chromatin remodellers together with DNA methylation, nucleosome positioning, histone modifcation and Hi-C chromosomal contacts to reveal that chro‑ matin remodellers can be stratifed into two functional groups. Group 1 (BRG1, SNF2H, CHD3 and CHD4) has a clear preference for binding at ‘actively marked’ chromatin and Group 2 (BRM, INO80, SNF2L and CHD1) for ‘repressively marked’ chromatin. We fnd that histone modifcations and chromatin architectural features, but not DNA methyla‑ tion, stratify the remodellers into these functional groups.

Conclusions: Our fndings suggest that chromatin remodelling events are synchronous and that chromatin remod‑ ellers themselves should be considered simultaneously and not as individual entities in isolation or necessarily by structural similarity, as they are traditionally classifed. Their coordinated function should be considered by preference for chromatin features in order to gain a more accurate and comprehensive picture of chromatin regulation.