生物
癌症研究
转录因子
下调和上调
肺癌
免疫沉淀
河马信号通路
抄写(语言学)
肿瘤进展
染色质免疫沉淀
细胞生物学
分子生物学
发起人
信号转导
癌症
基因
基因表达
遗传学
医学
肿瘤科
哲学
语言学
作者
Huixia Zhang,Shasha Li,Runxin Zhou,Tianqi Dong,Xiao Zhang,Man Yu,Jiaming Lin,Mingjun Shi,Ershuo Geng,Juebei Li,Ming‐Wei Wang,Liu Huang,Xiang‐Ping Yang,Shuguo Sun
标识
DOI:10.1016/j.canlet.2024.216667
摘要
The activation of YAP/TAZ, a pair of paralogs of transcriptional coactivators, initiates a dysregulated transcription program, which is a key feature of human cancer cells. However, it is not fully understood how YAP/TAZ promote dysregulated transcription for tumor progression. In this study, we employed the BioID method to identify the interactome of YAP/TAZ and discovered that YAP/TAZ interact with multiple components of SRCAP complex, a finding that was further validated through endogenous and exogenous co-immunoprecipitation, as well as immunofluorescence experiments. CUT&Tag analysis revealed that SRCAP complex facilitates the deposition of histone variant H2A.Z at target promoters. The depletion of SRCAP complex resulted in a decrease in H2A.Z occupancy and the oncogenic transcription of YAP/TAZ target genes. Additionally, the blockade of SRCAP complex suppressed YAP-driven tumor growth. In a genetically engineered lung adenocarcinoma mouse model and non-small cell lung cancer patients, SRCAP complex and H2A.Z deposition were found to be upregulated. This upregulation was statistically correlated with YAP expression, pathological stages, and poor survival in lung cancer patients. Together, our study uncovers that SRCAP complex plays a critical role in YAP/TAZ oncogenic transcription by coordinating H2A.Z deposition during cancer progression, providing potential targets for cancer diagnosis and prevention.
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