ChIP-seq and RNA-seq analysis of KMT2D-silenced metastatic melanoma cells. Homo sapiens

Purpose: Study of the mechanism trough which KTM2D regulates chromatin modification and transcription in a xenograft model of human metatstatic melanoma Methods: We generated patient derived xenografts (PDXs) from metastatic melanoma (MM) biopsies of three different patients. The MMs carry NRASQ61L, NRASQ61Q or BRAFV600 mutations. Cells from secondary PDX (PDX2) were transduced with lentiviral vectors carrying Luciferase (shLuc) and KMT2D (shKMT2D) hairpins and mRNA profiles and genome-wide chromatin-state maps were generated by deep sequencing using Illumina HiSeq2000. Results: we found that KMT2D regulates the activity of a subset of enhancers required for expression of specific genes. Overall design: Examination of KMT2D gDNA binding sites, 3 different histone modifications and expression profiles (RNA-seq) in PDX cells from 3 human metatastatic melanomas after KMT2D silencing