MLL1 is central to macrophage-mediated inflammation

In this issue of Blood, Sharma et al(1) demonstrate that gene transcription in macrophages contributes to the development of virus-associated coagulop-athy in mice infected with the murine coronavirus MHVA59, which was used as a surrogate for pulmonary SARS-CoV-2 infection in this study. Because coagulopathy is a major complication of SARS-CoV-2 infection, this mecha-nism of regulation may be relevant to the ongoing pandemic. In Sharma's study, transcriptional control is mediated through changes in chromatin structure wrought by the addition of a trimethyl group on the fourth lysine residue in the tail of histone 3 (H3K4Me3). Although many enzymes can set the H3K4Me3 mark, in this model the enzyme responsible is mixed lineage leukemia 1 (MLL1/KMT2a), which derives its name from gene rearrange-ments found in both lymphoblastic and myeloid leukemias. The team chose to assess the role of MLL1 in viral infection because previous studies have demonstrated its importance in macrophage activation (see figure).