Genome-wide profiling in colorectal cancer identifies PHF19 and TBC1D16 as oncogenic super enhancers.
Genome-wide profiling in colorectal cancer identifies PHF19 and TBC1D16 as oncogenic super enhancers.
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结直肠癌的全基因组分析将 PHF19 和 TBC1D16 确定为致癌超级增强子。
DOI：
10.1038/s41467-021-26600-5
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发表时间：
2021-11-04
影响因子：
16.6
通讯作者：
Wu M
中科院分区：
文献类型：
--
作者：
Li QL;Lin X;Yu YL;Chen L;Hu QX;Chen M;Cao N;Zhao C;Wang CY;Huang CW;Li LY;Ye M;Wu M
结直肠癌是世界上最常见的癌症之一。尽管基因组突变和单核苷酸多态性已被广泛研究，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，结合基因组和转录组学分析，我们使用ChIP-Seq在结直肠癌配对患者组织（来自相同患者的肿瘤和邻近组织）中在全基因组水平上分析活性增强子。总共，我们对73对结直肠癌组织进行了测序，并生成了147个H3 K27 ac ChIP-Seq，144个RNA-Seq，147个全基因组测序和86个H3 K4 me 3 ChIP-Seq样品。我们的分析确定了5590个增益和1100个丢失的变异增强子基因座在结直肠癌，334个增益和121个丢失的变异超级增强子基因座。模体分析和核心调控通路分析预测大肠癌中多个关键转录因子。进一步的实验验证了控制PHF 19和TBC 1D 16的超级增强子在调节结直肠癌肿瘤发生中的功能，并且KLF 3被鉴定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遗传学研究提供了重要的表观基因组资源和功能因子。活性增强子在结直肠癌（CRC）中的研究仍然不足。在本文中，作者使用基因组学、转录组学和表观基因组学分析了CRC患者中的活性增强子，鉴定并验证了变异的超级增强子位点以及作为相关转录因子的KLF 3。
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. Active enhancers are still understudied in colorectal cancers (CRC). Here the authors analyse active enhancers in CRC patients using genomics, transcriptomics, and epigenomics, identifying and validating variant super-enhancer loci as well as KLF3 as a relevant transcription factor.
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影响因子：
16
作者：
Calo, Eliezer;Wysocka, Joanna
通讯作者：
Wysocka, Joanna
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
5.2
作者：
Flebbe, Hannah;Hamdan, Feda H.;Grade, Marian
通讯作者：
Grade, Marian
影响因子：
64.5
作者：
Dowen JM;Fan ZP;Hnisz D;Ren G;Abraham BJ;Zhang LN;Weintraub AS;Schujiers J;Lee TI;Zhao K;Young RA
通讯作者：
Young RA
影响因子：
7
作者：
Hinoue, Toshinori;Weisenberger, Daniel J.;Laird, Peter W.
通讯作者：
Laird, Peter W.