首页|Topological reorganization and functional alteration of distinct genomic components in gallbladder cancer

Topological reorganization and functional alteration of distinct genomic components in gallbladder cancer

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Altered three-dimensional architecture of chromatin influences various genomic regulators and subsequent gene expression in human cancer.However,knowledge of the topological rearrangement of genomic hierarchical layers in cancer is largely limited.Here,by taking advantage of in situ Hi-C,RNA-sequencing,and chromatin immunoprecipitation sequencing(ChIP-seq),we investigated structural reorganization and functional changes in chromosomal compartments,topologically associated domains(TADs),and CCCTC binding factor(CTCF)-mediated loops in gallbladder cancer(GBC)tissues and cell lines.We observed that the chromosomal compartment A/B switch was correlated with CTCF binding levels and gene expression changes.Increased inter-TAD interactions with weaker TAD boundaries were identified in cancer cell lines relative to normal controls.Furthermore,the chromatin short loops and cancer unique loops associated with chromatin remodeling and epithelial-mesenchymal transition activation were enriched in cancer compared with their control counterparts.Cancer-specific enhancer-promoter loops,which contain multiple transcription factor binding motifs,actedas a central element to regulate aberrant gene expression.Depletion of individual enhancers in each loop anchor that connects with promoters led to the inhibition of their corresponding gene expressions.Collectively,our data offer the landscape of hierarchical layers of cancer genome and functional alterations that contribute to the development of GBC.

3D genomecancerTADsloopgene regulation

Guoqiang Li、Peng Pu、Mengqiao Pan、Xiaoling Weng、Shimei Qiu、Yiming Li、Sk Jahir Abbas、Lu Zou、Ke Liu、Zheng Wang、Ziyu Shao、Lin Jiang、Wenguang Wu、Yun Liu、Rong Shao、Fatao Liu、Yingbin Liu

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Department of Biliary-Pancreatic Surgery,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China

Shanghai Cancer Institute,State Key Laboratory of Oncogenes and Related Genes,Shanghai 200127,China

Shanghai Key Laboratory of Biliary Tract Disease,Shanghai 200082,China

Department of Health Science and Engineering,University of Shanghai for Science and Technology,Shanghai 200082,China

Shanghai Tenth People's Hospital of Tongji University,Shanghai 200072,China

Department of General Surgery,Xinhua Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200082,China

Department of Pharmacology,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China

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国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金National Science and Technology Major Projects for"Major New Drug Innovation and Development"Shanghai Sailing ProgramOpen Project Program of State Key Laboratory of Oncogenes and Related Genes

81874181819023613213000192919403052019ZX09301-15819YF1433000KF2120

2024

10.1007/s11684-023-1008-8

医学前沿
高等教育出版社

医学前沿

CSTPCD
影响因子：1.362
ISSN：2095-0217
年,卷(期)：2024.18(1)
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