Modification of the cancer-associated chromatin landscape in response to therapeutic DNA damage influences gene expression and contributes to cell fate. The central histone mark H2Bub1 results from addition of a single ubiquitin on lysine 120 of histone H2B and is an important regulator of gene expression. Following treatment with a platinum-based chemotherapeutic, there is a reduction in global levels of H2Bub1 accompanied by an increase in levels of the tumor suppressor p53. Although total H2Bub1 decreases following DNA damage, H2Bub1 is enriched downstream of transcription start sites of specific genes. Gene-specific H2Bub1 enrichment was observed at a defined group of genes that clustered into cancer-related pathways and correlated with increased gene expression. H2Bub1-enriched genes encompassed fifteen p53 target genes including PPM1D, BTG2, PLK2, MDM2, CDKN1A and BBC3, genes related to ERK/MAPK signalling, those participating in nucleotide excision repair including XPC, and genes involved in the immune response and platinum drug resistance including POLH. Enrichment of H2Bub1 at key cancer-related genes may function to regulate gene expression and influence the cellular response to therapeutic DNA damage.

响应治疗性DNA损伤而与癌症相关的染色质景观的修饰影响基因表达并有助于细胞命运。中心组蛋白标记H2Bub1是由于在组蛋白H2B的赖氨酸120上添加了单个泛素而产生的，并且是基因表达的重要调节剂。用铂基化学疗法治疗后，H2Bub1的总体水平降低，同时肿瘤抑制因子p53的水平升高。尽管总的H2Bub1在DNA损伤后减少，但H2Bub1在特定基因转录起始位点的下游富集。在一组特定的基因中观察到了基因特异的H2Bub1富集，这些基因聚集到癌症相关的途径中，并与增加的基因表达相关。富含H2Bub1的基因涵盖了15个p53靶基因，包括PPM1D，BTG2，PLK2，MDM2，CDKN1A和BBC3，与ERK / MAPK信号转导相关的基因，参与核苷酸切除修复的基因（包括XPC）以及涉及免疫应答和铂耐药性的基因（包括POLH）。H2Bub1在关键的癌症相关基因上的富集可能起到调节基因表达和影响细胞对治疗性DNA损伤的反应的作用。