Crosstalk of Histone Modifications in the Healthy Human Immune System

Abstract

Chromatin remodeling through post-translational modifications of histone tails (HPTM) is fundamental for regulation and maintenance of DNA-centered processes. Systems level understanding of coordination and interactions between HPTMs and their impact on the functional state of the immune cells remain unexplored due to the technical reasons. We leveraged large biologically heterogeneous data (>27 million cells), comprising of primary human immune cells profiled for 33 HPTMs and 4 histone variants at the single-cell level using high-dimensional mass cytometry (EpiTOF), to discover and map relations between HPTMs at the systems level. Briefly, we elucidated a comprehensive epigenetic network of HPTM interactions, discovered a novel subset of hematopoietic progenitors with distinct epigenetic profile, and revealed hitherto undescribed associations between a decrease in global methylations, modulation of one-carbon metabolism, and immune cell life span. Ultimately our work lays a foundation for future studies aimed at understanding complexity of HPTM interactions in immune response in infectious or autoimmune diseases, cancers, and vaccination.