Loss of grand histone H3 lysine 27 trimethylation domains mediated transcriptional activation in esophageal squamous cell carcinoma

Abstract Trimethylation of histone H3 lysine 27 trimethylation (H3K27me3) may be recruited by repressive Polycomb complexes to mediate gene silencing, which is critical for maintaining embryonic stem cell pluripotency and differentiation. However, the roles of aberrant H3K27me3 patterns in tumorigen...

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Autores principales:	Jian Yuan, Qi Jiang, Tongyang Gong, Dandan Fan, Ji Zhang, Fukun Chen, Xiaolin Zhu, Xinyu Wang, Yunbo Qiao, Hongyan Chen, Zhihua Liu, Jianzhong Su
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/7e95ae9d883948b0bed0b14b04be523f
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spelling	oai:doaj.org-article:7e95ae9d883948b0bed0b14b04be523f2021-12-02T18:50:45ZLoss of grand histone H3 lysine 27 trimethylation domains mediated transcriptional activation in esophageal squamous cell carcinoma10.1038/s41525-021-00232-62056-7944https://doaj.org/article/7e95ae9d883948b0bed0b14b04be523f2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00232-6https://doaj.org/toc/2056-7944Abstract Trimethylation of histone H3 lysine 27 trimethylation (H3K27me3) may be recruited by repressive Polycomb complexes to mediate gene silencing, which is critical for maintaining embryonic stem cell pluripotency and differentiation. However, the roles of aberrant H3K27me3 patterns in tumorigenesis are not fully understood. Here, we discovered that grand silencer domains (breadth > 50 kb) for H3K27me3 were significantly associated with epithelial cell differentiation and exhibited high gene essentiality and conservation in human esophageal epithelial cells. These grand H3K27me3 domains exhibited high modification signals involved in gene silencing, and preferentially occupied the entirety of topologically associating domains and interact with each other. We found that widespread loss of the grand H3K27me3 domains in of esophageal squamous cell carcinomas (ESCCs) were enriched in genes involved in epithelium and endothelium differentiation, which were significantly associated with overexpression with increase of active modifications of H3K4me3, H3K4me1, and H3K27ac marks, as well as DNA hypermethylation in the gene bodies. A total of 208 activated genes with loss of grand H3K27me3 domains in ESCC were identified, where the higher expression and mutation of T-box transcription factor 20 (TBX20) were associated with worse patients’ outcomes. Our results showed that knockdown of TBX20 may have led to a striking defect in esophageal cancer cell growth and carcinogenesis-related pathway, including cell cycle and homologous recombination. Together, our results reveal that loss of grand H3K27me3 domains represent a catalog of remarkable activating regulators involved in carcinogenesis.Jian YuanQi JiangTongyang GongDandan FanJi ZhangFukun ChenXiaolin ZhuXinyu WangYunbo QiaoHongyan ChenZhihua LiuJianzhong SuNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Jian Yuan Qi Jiang Tongyang Gong Dandan Fan Ji Zhang Fukun Chen Xiaolin Zhu Xinyu Wang Yunbo Qiao Hongyan Chen Zhihua Liu Jianzhong Su Loss of grand histone H3 lysine 27 trimethylation domains mediated transcriptional activation in esophageal squamous cell carcinoma
description	Abstract Trimethylation of histone H3 lysine 27 trimethylation (H3K27me3) may be recruited by repressive Polycomb complexes to mediate gene silencing, which is critical for maintaining embryonic stem cell pluripotency and differentiation. However, the roles of aberrant H3K27me3 patterns in tumorigenesis are not fully understood. Here, we discovered that grand silencer domains (breadth > 50 kb) for H3K27me3 were significantly associated with epithelial cell differentiation and exhibited high gene essentiality and conservation in human esophageal epithelial cells. These grand H3K27me3 domains exhibited high modification signals involved in gene silencing, and preferentially occupied the entirety of topologically associating domains and interact with each other. We found that widespread loss of the grand H3K27me3 domains in of esophageal squamous cell carcinomas (ESCCs) were enriched in genes involved in epithelium and endothelium differentiation, which were significantly associated with overexpression with increase of active modifications of H3K4me3, H3K4me1, and H3K27ac marks, as well as DNA hypermethylation in the gene bodies. A total of 208 activated genes with loss of grand H3K27me3 domains in ESCC were identified, where the higher expression and mutation of T-box transcription factor 20 (TBX20) were associated with worse patients’ outcomes. Our results showed that knockdown of TBX20 may have led to a striking defect in esophageal cancer cell growth and carcinogenesis-related pathway, including cell cycle and homologous recombination. Together, our results reveal that loss of grand H3K27me3 domains represent a catalog of remarkable activating regulators involved in carcinogenesis.
format	article
author	Jian Yuan Qi Jiang Tongyang Gong Dandan Fan Ji Zhang Fukun Chen Xiaolin Zhu Xinyu Wang Yunbo Qiao Hongyan Chen Zhihua Liu Jianzhong Su
author_facet	Jian Yuan Qi Jiang Tongyang Gong Dandan Fan Ji Zhang Fukun Chen Xiaolin Zhu Xinyu Wang Yunbo Qiao Hongyan Chen Zhihua Liu Jianzhong Su
author_sort	Jian Yuan
title	Loss of grand histone H3 lysine 27 trimethylation domains mediated transcriptional activation in esophageal squamous cell carcinoma
title_short	Loss of grand histone H3 lysine 27 trimethylation domains mediated transcriptional activation in esophageal squamous cell carcinoma
title_full	Loss of grand histone H3 lysine 27 trimethylation domains mediated transcriptional activation in esophageal squamous cell carcinoma
title_fullStr	Loss of grand histone H3 lysine 27 trimethylation domains mediated transcriptional activation in esophageal squamous cell carcinoma
title_full_unstemmed	Loss of grand histone H3 lysine 27 trimethylation domains mediated transcriptional activation in esophageal squamous cell carcinoma
title_sort	loss of grand histone h3 lysine 27 trimethylation domains mediated transcriptional activation in esophageal squamous cell carcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7e95ae9d883948b0bed0b14b04be523f
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_version_	1718377514443735040

Loss of grand histone H3 lysine 27 trimethylation domains mediated transcriptional activation in esophageal squamous cell carcinoma

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