Genetic and epigenetic mutations have both been implicated to have a driving role in the development of cancer. The epigenetic regulator KMT2D is one of the most mutated genes across all cancers in TCGA, the cancer genome atlas. In particular, KMT2D loss-of-function mutations (LOF) are present in 90% of follicular lymphomas (FL) and 40% of diffuse large B cell lymphoma (DLBCL), indicating it may be an important tumour suppressor in non-Hodgkin lymphomas (NHL). KMT2D is a histone methyltransferase that deposits activating H3K4me1 marks on nucleosomes flanking enhancer regions. Our lab performed ChIP-sequencing analyses within human embryonic kidney cells (HEK293A) and showed that loss of KMT2D results in a decrease of H3K4me1 and H3K27ac marks at KMT2D-dependant active enhancers, resulting in decreased transcription of their target genes. A gene ontology analysis showed that genes affected by KMT2D loss were enriched within the retinoic acid and TGF-b pathways, while their promoter regions were enriched with DNA binding motifs corresponding to TGF-b signalling co-activator complex AP-1. We currently aim to validate these findings in other relevant cell types.

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