KMT2D regulates Fanconi anemia pathway genes through regulating promoters/enhances upon glucose deprivation (CHIPseq)

Histone H3 lysine (H3K4) methyltransferase KMT2D is a key regulator of gene expression, mainly through promoting H3K4 methylation and activating enhancers, and plays critical roles in development, differentiation, metabolism, and tumor suppression. Here, our study showed that KMT2D was recruited to the enhancer regions of several Fanconi anemia (FA) pathway genes, such as ATR, FANCM, REV3L, and TOP3A, in response to glucose deprivation. Notably, KMT2D loss led to significant impairment of promoter/enhancer signals, as evidenced by decreased H3K4me1, H3K4me3, and H3K27ac signals, on several FA pathway genes. Our ChIP-Seq results demonstrated that the inactivation of promoters/enhancers due to KMT2D loss is a key contributor to the downregulation of FA pathway genes in glucose-deprived KMT2D-deficient HNSCC. Overall design: Chromatin binding profiling of KMT2D in wild-type SCC23 HNSCC cells with glucose deprivation treatment for 6 hours (-Glc). Chromatin binding profiling of histone modification H3K4me1, H3K27ac, H3K4me3, H3K9me3, and H3K27me3 in WT and KMT2D knockout (KMT2D-KO) SCC23 HNSCC cells under glucose deprivation treatment for 6 hours (-Glc).