Dynamic Chromatin States Coupling with Key Transcription Factors in Colitis-Associated Colorectal Cancer.
Dynamic Chromatin States Coupling with Key Transcription Factors in Colitis-Associated Colorectal Cancer.
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动态染色质与结肠炎相关结直肠癌的关键转录因子耦合。
DOI：
10.1002/advs.202200536
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发表时间：
2022-08
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炎症是结直肠癌的重要危险因素之一。然而，从结肠炎转变为结直肠癌的机制仍然难以捉摸。最近，表观遗传学变化已成为结肠炎相关癌症的重要调控因素。在此，我们在AOM-DSS诱导的结直肠癌小鼠模型中对组蛋白修饰进行了系统的表观基因组学研究，包括H3K4me1、H3K4me3、H3K27ac、H3K27me3和H3K9me3。结合转录数据，作者生成了一个由105个深度测序文件组成的数据集，并说明了炎症-癌症过渡过程中五个时间点染色质状态的动态景观。根据动态转录和表观基因组信息识别功能基因簇，并说明了这一过程中的关键信号通路。这项研究的结果表明，增强子状态区域在炎症-癌症转化过程中发挥着重要作用。它根据增强子信息预测新的转录因子，并实验证明OTX2是一个关键的肿瘤抑制转录因子。综上所述，这项研究提供了全面的表观基因组数据，并揭示了结肠炎相关癌症的新分子机制。在结肠炎相关癌症模型中，研究了从炎症向癌症转变过程中染色质状态的动态变化。多重组学分析表明，增强子状态区域在炎症-癌症转化过程中发挥着重要作用。新的转录因子，如OTX2，被发现是结直肠癌的关键因子。
Inflammation is one of the critical risk factors for colorectal cancer (CRC). However, the mechanisms for transition from colitis to CRC remain elusive. Recently, epigenetic changes have emerged as important regulatory factors for colitis‐associated cancer. Here, a systematic epigenomic study of histone modifications is performed, including H3K4me1, H3K4me3, H3K27ac, H3K27me3 and H3K9me3, in an AOM‐DSS‐induced CRC mouse model. In combination with transcriptomic data, the authors generate a dataset of 105 deep sequencing files and illustrate the dynamic landscape of chromatin states at five time points during inflammation‐cancer transition. Functional gene clusters are identified based on dynamic transcriptomic and epigenomic information, and key signaling pathways in the process are illustrated. This study's results reveal that enhancer state regions play important roles during inflammation‐cancer transition. It predicts novel transcription factors based on enhancer information, and experimentally proves OTX2 as a critical tumor suppressive transcription factor. Taken together, this study provides comprehensive epigenomic data and reveals novel molecular mechanisms for colitis‐associated cancer. The dynamic changes of chromatin states during the transition from inflammation to cancer are studied in a colitis‐associated cancer model. Multiple omics analysis reveal that enhancer state regions play important roles during inflammation‐cancer transition. Novel transcription factors, such as OTX2, are discovered as critical factors for colorectal cancer.