Frontier Science Center for Immunology and Metabolism, RNA Institute, Hubei Key Laboratory of Cell Homeostasis, Hubei Key Laboratory of Developmentally Originated Disease, Hubei Key Laboratory of Intestinal and Colorectal Diseases, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, China.
Division of Gastroenterology, Department of Geriatrics, Hubei Clinical Centre & Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430072, China.
Nat Commun. 2021 Nov 4;12(1):6407. doi: 10.1038/s41467-021-26600-5.
Colorectal cancer is one of the most common cancers in the world. Although genomic mutations and single nucleotide polymorphisms have been extensively studied, the epigenomic status in colorectal cancer patient tissues remains elusive. Here, together with genomic and transcriptomic analysis, we use ChIP-Seq to profile active enhancers at the genome wide level in colorectal cancer paired patient tissues (tumor and adjacent tissues from the same patients). In total, we sequence 73 pairs of colorectal cancer tissues and generate 147 H3K27ac ChIP-Seq, 144 RNA-Seq, 147 whole genome sequencing and 86 H3K4me3 ChIP-Seq samples. Our analysis identifies 5590 gain and 1100 lost variant enhancer loci in colorectal cancer, and 334 gain and 121 lost variant super enhancer loci. Multiple key transcription factors in colorectal cancer are predicted with motif analysis and core regulatory circuitry analysis. Further experiments verify the function of the super enhancers governing PHF19 and TBC1D16 in regulating colorectal cancer tumorigenesis, and KLF3 is identified as an oncogenic transcription factor in colorectal cancer. Taken together, our work provides an important epigenomic resource and functional factors for epigenetic studies in colorectal cancer.
结直肠癌是世界上最常见的癌症之一。尽管已经广泛研究了基因组突变和单核苷酸多态性，但结直肠癌患者组织中的表观基因组状态仍然难以捉摸。在这里，我们结合基因组和转录组分析，使用 ChIP-Seq 对结直肠癌配对患者组织（来自同一患者的肿瘤和相邻组织）中的全基因组水平的活性增强子进行了描绘。总共，我们对 73 对结直肠癌组织进行了测序，生成了 147 个 H3K27ac ChIP-Seq、144 个 RNA-Seq、147 个全基因组测序和 86 个 H3K4me3 ChIP-Seq 样本。我们的分析确定了结直肠癌中 5590 个增益和 1100 个丢失的变体增强子位点，以及 334 个增益和 121 个丢失的变体超级增强子位点。通过 motif 分析和核心调控回路分析预测了结直肠癌中的多个关键转录因子。进一步的实验验证了超级增强子调控 PHF19 和 TBC1D16 调节结直肠癌肿瘤发生的功能，并且鉴定 KLF3 为结直肠癌中的致癌转录因子。总之，我们的工作为结直肠癌的表观基因组研究提供了重要的表观基因组资源和功能因素。
