Genome-Wide Enhancer Analysis Reveals the Role of AP-1 Transcription Factor in Head and Neck Squamous Cell Carcinoma.

Genome-Wide Enhancer Analysis Reveals the Role of AP-1 Transcription Factor in Head and Neck Squamous Cell Carcinoma.
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全基因组增强子分析揭示了 AP-1 转录因子在头颈鳞状细胞癌中的作用。

DOI:
10.3389/fmolb.2021.701531
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发表时间:
2021
影响因子:
5
通讯作者:
Li LY
Li LY
中科院分区:
生物学3区
文献类型:
--
作者:
Wang CY;Yu GT;Gao C;Chen J;Li QL;Zhang L;Wu M;Sun ZJ;Li LY

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头颈部鳞状细胞癌(HNSCC)是世界上最常见的癌症之一,但其表观基因组特征尚未确定。在这里,我们通过使用Tgfbr 1/Pten双条件性敲除HNSCC小鼠模型进行H3 K27 ac和H3 K4 me 1 ChIP-Seq来研究HNSCC头部肿瘤组织的活性增强子的染色质景观。我们鉴定了1,248个增益变体增强子基因座(VEL)和2,188个丢失的VEL,以及153个增益变体超级增强子基因座(VSEL)和234个丢失的VSEL。通过基序分析预测了可能参与的转录因子,我们确定AP-1是HNSCC和许多其他类型癌症中的关键致癌转录因子之一。结合转录组学和表观基因组学数据,我们的分析还表明,AP-1和组蛋白修饰协调调节HNSCC中靶基因的表达。总之,我们的研究为HNSCC增强子的研究提供了重要的表观基因组信息,并揭示了AP-1调控HNSCC的新机制。
Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world, but its epigenomic features have not been determined. Here, we studied the chromatin landscape of active enhancers of HNSCC head tumor tissues by performing H3K27ac and H3K4me1 ChIP-Seq with a Tgfbr1/Pten double conditional knockout HNSCC mouse model. We identified 1,248 gain variant enhancer loci (VELs) and 2,188 lost VELs, as well as 153 gain variant super enhancer loci (VSELs) and 234 lost VSELs. Potentially involved transcription factors were predicted with motif analysis, and we identified AP-1 as one of the critical oncogenic transcription factors in HNSCC and many other types of cancer. Combining transcriptomic and epigenomic data, our analysis also showed that AP-1 and histone modifications coordinately regulate target gene expression in HNSCC. In conclusion, our study provides important epigenomic information for enhancer studies in HNSCC and reveals new mechanism for AP-1 regulating HNSCC.
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