Another histone modification found

Recent research has suggested that lactate may have regulatory effects, but the mechanism was not clear. Now, a team led by Lev Becker and Yingming Zhao of the University of Chicago shows that it may exert those effects by chemically modifying histones—the protein spools that DNA is wrapped around. The researchers used high-performance liquid chromatography/mass spectrometry to identify 28 sites at which lactate was attached to lysine residues in histone proteins (Nature 2019, DOI: 10.1038/s41586-019-1678-1). “Lactate is an emerging metabolite regulating several immune functions,” says Claudio Mauro, a researcher at the Institute of Inflammation and Ageing at the University of Birmingham, who was not involved in the research. “This is the first report of lactate epigenetic modifications.” In the current study, the researchers exposed cells to low oxygen levels and bacteria and found that both lead to increased histone lactylation. In macrophages, a type of immune cell, lactylation turned on genes involved in wound healing. The researchers suggest that histone lactylation helps maintain homeostasis.