11 种肿瘤类型的癌症转变过程中的表观遗传调控。
Epigenetic regulation during cancer transitions across 11 tumour types.
发表日期：2023 Nov 01
作者：
Nadezhda V Terekhanova, Alla Karpova, Wen-Wei Liang, Alexander Strzalkowski, Siqi Chen, Yize Li, Austin N Southard-Smith, Michael D Iglesia, Michael C Wendl, Reyka G Jayasinghe, Jingxian Liu, Yizhe Song, Song Cao, Andrew Houston, Xiuting Liu, Matthew A Wyczalkowski, Rita Jui-Hsien Lu, Wagma Caravan, Andrew Shinkle, Nataly Naser Al Deen, John M Herndon, Jacqueline Mudd, Cong Ma, Hirak Sarkar, Kazuhito Sato, Omar M Ibrahim, Chia-Kuei Mo, Sara E Chasnoff, Eduard Porta-Pardo, Jason M Held, Russell Pachynski, Julie K Schwarz, William E Gillanders, Albert H Kim, Ravi Vij, John F DiPersio, Sidharth V Puram, Milan G Chheda, Katherine C Fuh, David G DeNardo, Ryan C Fields, Feng Chen, Benjamin J Raphael, Li Ding
来源：
Epigenetics & Chromatin
摘要：
染色质可及性对于调节基因表达和细胞身份至关重要，可及性的改变与驱动癌症的发生、进展和转移有关1-4。尽管已经研究了遗传对致癌转变的贡献，但表观遗传驱动因素仍然知之甚少。在这里，我们使用 225 个样本的单核染色质可及性数据（使用转座酶可及染色质的单核测定）构建了泛癌表观遗传和转录组图谱，并使用 206 个样本的匹配单细胞或单核 RNA 测序表达数据。通过富集可及的染色质区域、转录因子基序和调节子，对每个平台超过 100 万个细胞进行分析，我们确定了与癌症转变相关的表观遗传驱动因素。一些表观遗传驱动因素出现在多种癌症中（例如，ABCC1 和 VEGFA 的调节区域；GATA6 和 FOX 家族基序），而另一些则是癌症特异性的（例如，FGF19、ASAP2 和 EN1 的调节区域以及 PBX3 基序）。在表观遗传改变的途径中，TP53、缺氧和 TNF 信号传导与癌症发生有关，而雌激素反应、上皮-间质转化和顶端连接与转移转变有关。此外，我们揭示了增强子可及性和基因表达之间的显着相关性，并揭示了表观遗传和遗传驱动因素之间的合作。该图谱为进一步研究癌症转变中的表观遗传动力学奠定了基础。© 2023。作者。
Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis1-4. Although the genetic contributions to oncogenic transitions have been investigated, epigenetic drivers remain less understood. Here we constructed a pan-cancer epigenetic and transcriptomic atlas using single-nucleus chromatin accessibility data (using single-nucleus assay for transposase-accessible chromatin) from 225 samples and matched single-cell or single-nucleus RNA-sequencing expression data from 206 samples. With over 1 million cells from each platform analysed through the enrichment of accessible chromatin regions, transcription factor motifs and regulons, we identified epigenetic drivers associated with cancer transitions. Some epigenetic drivers appeared in multiple cancers (for example, regulatory regions of ABCC1 and VEGFA; GATA6 and FOX-family motifs), whereas others were cancer specific (for example, regulatory regions of FGF19, ASAP2 and EN1, and the PBX3 motif). Among epigenetically altered pathways, TP53, hypoxia and TNF signalling were linked to cancer initiation, whereas oestrogen response, epithelial-mesenchymal transition and apical junction were tied to metastatic transition. Furthermore, we revealed a marked correlation between enhancer accessibility and gene expression and uncovered cooperation between epigenetic and genetic drivers. This atlas provides a foundation for further investigation of epigenetic dynamics in cancer transitions.© 2023. The Author(s).