Suv39h-catalysed H3K9me3 is critical for euchromatic genome organisation and the maintenance of gene transcription

Abstract

Summary H3K9me3-dependent heterochromatin is critical for the silencing of repeat-rich pericentromeric regions and also has key roles in repressing lineage-inappropriate protein-coding genes in differentiation and development. Here, we investigate the molecular consequences of heterochromatin loss in cells deficient in both Suv39h1 and Suv39h2 (Suv39DKO), the major mammalian histone methyltransferase enzymes that catalyse heterochromatic H3K9me3 deposition. Unexpectedly, we reveal a predominant repression of protein-coding genes in Suv39DKO cells, with these differentially expressed genes principally in euchromatic (DNaseI-accessible, H3K27ac-marked) rather than heterochromatic (H3K9me3-mark..