Epigenetic profiling of the three-stage thymic development pathway of MAIT cells, focusing on H3K27 acetylation 3408

Abstract Description T-cell development is a highly regulated process in which epigenetic modifications play a pivotal role in all stages of development. Among these modifications, acetylation of histone H3 at lysine 27 (H3K27ac) is a marker of active chromatin and is strongly associated with active transcription. Mucosal-associated invariant T cells (MAIT) are an unconventional T cell subset that expresses a unique semi-invariant T cell receptor that enables MAIT cells to recognise vitamin B metabolites of microbes presented by MHC class I-related protein molecules. Previous research has focused on epigenetic regulation in T cell subsets, such as mouse iNKT cells; however, epigenetic regulation of human MAIT cell development remains unexplored. In this study, we mapped the regulatory chromatin landscape during the development of human MAIT cells to identify promoters and distal elements that play a role in this process. Genome-wide distribution of H3K27ac was generated using CUTnTAG and sequencing in thymic MAIT cells at stages 1, 2, and 3 and combined with transcriptome data. We found that dynamic H3K27ac peaks at promoters and distal elements were highly correlated with gene expression changes from S1 to S3 during MAIT cell differentiation. Sequencing results indicated a noticeable increase in H3K27ac from stage 1 to stage 3 in specific transcription factor (TF) genes, such as PLZF. Our work in the context of human MAIT cells recognises new genes that regulate the development of these cells. Funding Sources This research is supported by the Sylvia & Charles Viertel Fellowship research and NHMRC grant (2030186). Topic Categories Hematopoiesis and Immune System Development (HEM)