Segal Tamar, Salmon-Divon Mali, Gerlitz Gabi
Department of Molecular Biology, Faculty of Life Sciences and Ariel Center for Applied Cancer Research, Ariel University, Ariel 40700, Israel.
Cells. 2018 Nov 9;7(11):205. doi: 10.3390/cells7110205.
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.
H3K9me3、H3K27me3和H4K20me1是与染色质凝聚和转录抑制相关的表观遗传标记。此前，我们发现黑色素瘤细胞的迁移与整体染色质凝聚相关且依赖于整体染色质凝聚，其中包括这些标记的整体增加。结合其他人最近的报道表明这是迁移细胞的一个普遍特征。在这里，为了了解这些标记在迁移细胞中的功能，我们通过ChIP-seq分析对它们进行了定位。该分析表明，迁移的诱导导致这些标记在基因组上的扩展以及它们之间重叠的增加。值得注意的是，迁移的诱导导致重复元件处的H3K9me3和H4K20me1信号比蛋白质编码基因处有更高的增加，而H3K27me3则呈现相反的模式。转录组分析显示，迁移诱导后有182个基因发生改变，其中33%的这些变化依赖于H3K27me3。在迁移诱导时，还需要H3K27me3来防止另外501个基因的表达发生变化。综上所述，我们的结果表明，迁移细胞中的异染色质化是全局性的，并不局限于特定的基因组位点，并且H3K27me3是执行迁移特异性转录计划的关键组成部分。
