Circadian clock function does not require the histone methyltransferase MLL3

• DOI: 10.1096/fj.202200368r
• Publication Date: 2022-06-15T14:54:46Z
• Authors: Matthew Baxter; Toryn Poolman; Peter Cunningham; Louise Hunter; Maria Voronkov; Gareth B. Kitchen; Laurence Goosey; Nicola Begley; Danielle Kay; Abby Hespe; Robert Maidstone; Andrew S. I. Loudon; David W. Ray
• Keywords: H3K4me3; Histone H4; Histone Methylation

Abstract The circadian clock controls the physiological function of tissues through regulation thousands genes in a cell‐type‐specific manner. core cellular is transcription–translation negative feedback loop, which can recruit epigenetic regulators to facilitate temporal control gene expression. Histone methyltransferase, mixed lineage leukemia 3 (MLL3) was reported be required for maintenance oscillations cultured cells. Here, we test role MLL3 organization whole animals. Using mice expressing catalytically inactive MLL3, show that methyltransferase activity fact not vitro range tissues, nor behavioral rhythms vivo. In contrast previous report, loss MLL3‐dependent methylation did affect global levels H3K4 liver, indicating substantial compensation from other methyltransferases. Furthermore, found little evidence genomic repositioning H3K4me3 marks. We did, however, observe H3K4me1 intronic regions intergenic and promoters; there were no changes mark abundance around genes. Output functions clock, such as inflammation, largely intact MLL3‐methyltransferase‐deficient mice, although some gene‐specific observed, with sexually dimorphic specific cytokines. Taken together, these observations indicate MLL3‐directed histone essential function; it may influence inflammatory response.