The Heterochromatin Landscape in Migrating Cells and the Importance of H3K27me3 for Associated Transcriptome Alterations

Abstract

H3K9me3, H3K27me3, and H4K20me1 are epigenetic markers associated with chromatin condensation and transcriptional repression. Previously, we found that migration of melanoma cells is associated with and dependent on global chromatin condensation that includes a global increase in these markers. Taken together with more recent reports by others suggests it is a general signature of migrating cells. Here, to learn about the function of these markers in migrating cells, we mapped them by ChIP-seq analysis. This analysis revealed that induction of migration leads to expansion of these markers along the genome and to an increased overlapping between them. Significantly, induction of migration led to a higher increase in H3K9me3 and H4K20me1 signals at repetitive elements than at protein-coding genes, while an opposite pattern was found for H3K27me3. Transcriptome analysis revealed 182 altered genes following induction of migration, of which 33% are dependent on H3K27me3 for these changes. H3K27me3 was also required to prevent changes in the expression of 501 other genes upon induction of migration. Taken together, our results suggest that heterochromatinization in migrating cells is global and not restricted to specific genomic loci and that H3K27me3 is a key component in executing a migration-specific transcriptional plan.