Abstract
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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is one of the most common human malignancies in the world, with poor prognosis for patients (Leemans et al, 2018)
Activation of enhancers for oncogenes and repression of enhancers for tumor suppressors are important for tumor cell transformation
We investigated the genome-wide distribution of active enhancers in an HNSCC model and identified 1,248 gain VELs and 2,188 lost VELs, as well as 153 gain VSELs and 234 lost VSELs
Summary
Head and neck squamous cell carcinoma (HNSCC) is one of the most common human malignancies in the world, with poor prognosis for patients (Leemans et al, 2018). Specific patterns of histone modifications occupy the surrounding nucleosomes of enhancers, which are often used to identify novel enhancers. If H3K27ac is Genome-Wide Enhancer Analysis in HNSCC present, the enhancer is active; if H3K27me occupies the region instead of H3K27ac, the enhancer is poised (Shlyueva et al, 2014; Nizovtseva et al, 2017). One study on mouse embryonic stem cells identified 25,036 enhancers using chromatin regions enriched with H3K4me (Creyghton et al, 2010). Their results indicated H3K27ac as an active enhancer hallmark. H3K27ac and H3K4me are hallmarks for active promoters of expressed gene; only H3K27ac-enriched regions far away from promoters are considered as active enhancers (Rickels and Shilatifard, 2018)
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