Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing 211166, China.
Genes (Basel). 2024 Jul 26;15(8):988. doi: 10.3390/genes15080988.
Eukaryotic genomes are organized into chromatin domains through long-range chromatin interactions which are mediated by the binding of architectural proteins, such as CTCF and cohesin, and histone modifications. Based on the published Hi-C and ChIP-seq datasets in human monocyte-derived macrophages, we identified 206 and 127 differential chromatin interactions (DCIs) that were not located within transcription readthrough regions in influenza A virus- and interferon β-treated cells, respectively, and found that the binding positions of CTCF and RAD21 within more than half of the DCI sites did not change. However, five histone modifications, H3K4me3, H3K27ac, H3K36me3, H3K9me3, and H3K27me3, showed significantly more dramatic changes than CTCF and RAD21 within the DCI sites. For H3K4me3, H3K27ac, H3K36me3, and H3K27me3, significantly more dramatic changes were observed outside than within the DCI sites. We further applied a motif scanning approach to discover proteins that might correlate with changes in histone modifications and chromatin interactions and found that PRDM9, ZNF384, and STAT2 frequently bound to DNA sequences corresponding to 1 kb genomic intervals with gains or losses of a histone modification within the DCI sites. This study explores the dynamic regulation of chromatin interactions and extends the current knowledge of the relationship between histone modifications and chromatin interactions.
真核生物基因组通过长距离染色质相互作用组织成染色质域，这些相互作用由结构蛋白（如 CTCF 和黏连蛋白）和组蛋白修饰介导。基于已发表的人类单核细胞衍生巨噬细胞中的 Hi-C 和 ChIP-seq 数据集，我们分别在甲型流感病毒和干扰素 β 处理的细胞中鉴定出 206 个和 127 个差异染色质相互作用（DCIs），这些相互作用不位于转录通读区域内，并且发现 CTCF 和 RAD21 在超过一半的 DCI 位点的结合位置没有改变。然而，五种组蛋白修饰（H3K4me3、H3K27ac、H3K36me3、H3K9me3 和 H3K27me3）在 DCI 位点内的变化明显比 CTCF 和 RAD21 更为显著。对于 H3K4me3、H3K27ac、H3K36me3 和 H3K27me3，在 DCI 位点外观察到的变化明显比在 DCI 位点内更为显著。我们进一步应用 motif 扫描方法来发现可能与组蛋白修饰和染色质相互作用变化相关的蛋白质，发现 PRDM9、ZNF384 和 STAT2 经常与 DNA 序列结合，这些序列对应于 DCI 位点内获得或失去组蛋白修饰的 1kb 基因组间隔。本研究探讨了染色质相互作用的动态调控，并扩展了组蛋白修饰与染色质相互作用之间关系的现有知识。
