MHC I级
生物
脱氮酶
细胞生物学
主要组织相容性复合体
PRC2
表观遗传学
泛素
CD8型
癌症研究
分子生物学
免疫系统
遗传学
组蛋白H3
基因
作者
Ruud H. Wijdeven,Sietse J. Luk,Tom A. W. Schoufour,Sabina Y. van der Zanden,Marta Cabezuelo,Mirjam H. M. Heemskerk,Jacques Neefjes
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2023-12-13
卷期号:212 (3): 446-454
标识
DOI:10.4049/jimmunol.2300263
摘要
Abstract MHC class I (MHC-I) molecules are critical for CD8+ T cell responses to viral infections and malignant cells, and tumors can downregulate MHC-I expression to promote immune evasion. In this study, using a genome-wide CRISPR screen on a human melanoma cell line, we identified the polycomb repressive complex 1 (PRC1) subunit PCGF1 and the deubiquitinating enzyme BAP1 as opposite regulators of MHC-I transcription. PCGF1 facilitates deposition of ubiquitin at H2AK119 at the MHC-I promoters to silence MHC-I, whereas BAP1 removes this modification to restore MHC-I expression. PCGF1 is widely expressed in tumors and its depletion increased MHC-I expression in multiple tumor lines, including MHC-Ilow tumors. In cells characterized by poor MHC-I expression, PRC1 and PRC2 act in parallel to impinge low transcription. However, PCGF1 depletion was sufficient to increase MHC-I expression and restore T cell–mediated killing of the tumor cells. Taken together, our data provide an additional layer of regulation of MHC-I expression in tumors: epigenetic silencing by PRC1 subunit PCGF1.
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