GLIS2 promotes colorectal cancer through repressing enhancer activation
GLIS2 promotes colorectal cancer through repressing enhancer activation
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GLIS2通过抑制增强子激活促进结直肠癌
DOI：
10.1038/s41389-020-0240-1
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发表时间：
2020
期刊：
影响因子：
6.2
通讯作者：
Min Wu
中科院分区：
文献类型：
--
作者：
Jie Yao;Pin-Ji Lei;Qing-Lan Li;Ji Chen;Shan-Bo Tang;Qiong Xiao;Xiang Lin;Xiang Wang;Lian-Yun Li;Min Wu
基因转录受多种转录因子的协同调控。然而，仍然缺乏一个系统的方法来确定转录因子的共调节因子。在这里，我们进行了ChIP-Seq分析并预测了p53介导的转录过程的调节因子，从而证实了GLIS 2、MAZ和MEF 2A在调节p53靶基因中的作用。我们发现，GLIS 2选择性地调节PUMA的转录，而不是p21。GLIS 2缺陷导致PUMA增强子上H3 K27 ac和p53结合增强，促进PUMA表达。增加细胞凋亡率，但不增加细胞周期。此外，GLIS 2通过抑制p300抑制增强子上的H3 K27 ac水平，调节与粘着斑相关的基因表达，促进细胞迁移。大数据分析支持GLIS 2作为结肠癌的致癌基因，也许还有其他癌症。综上所述，我们预测了p53转录调节因子的候选者，并通过抑制增强子激活为GLIS 2作为癌基因提供了证据。
Gene transcription is coordinately regulated by multiple transcription factors. However, a systematic approach is still lacking to identify co-regulators for transcription factors. Here, we performed ChIP-Seq analysis and predicted the regulators for p53-mediated transcription process, from which we confirmed the roles of GLIS2, MAZ and MEF2A in regulating p53 target genes. We revealed that GLIS2 selectively regulates the transcription ofPUMAbut notp21. GLIS2 deficiency caused the elevation of H3K27ac and p53 binding on thePUMAenhancer, and promotedPUMAexpression. It increased the rate of apoptosis, but not cell cycle. Moreover, GLIS2 represses H3K27ac level on enhancers, regulates the gene expression related with focal adhesion and promotes cell migration, through inhibiting p300. Big data analysis supportsGLIS2as an oncogene in colon cancer, and perhaps other cancers. Taken together, we have predicted candidates for p53 transcriptional regulators, and provided evidence forGLIS2as an oncogene through repressing enhancer activation.