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DOI | 10.1038/s41467-017-00349-2 |
PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma | |
Bleu, Melusine1; Gaulis, Swann1,11; Lopes, Rui1; Sprouffske, Kathleen1; Apfel, Verena1; Holwerda, Sjoerd2,11; Pregnolato, Marco1,5,6; Yildiz, Umut1,7; Cordo, Valentina1,8; Dost, Antonella F. M.1,9,10; Knehr, Judith2; Carbone, Walter2; Lohmann, Felix2,11; Lin, Charles Y.3; Bradner, James E.4; Kauffmann, Audrey1; Tordella, Luca1; Roma, Guglielmo2; Galli, Giorgio G.1 | |
2019-08-20 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | Switzerland; USA; Germany; Netherlands |
英文摘要 | Transcription factor networks shape the gene expression programs responsible for normal cell identity and pathogenic state. Using Core Regulatory Circuitry analysis (CRC), we identify PAX8 as a candidate oncogene in Renal Cell Carcinoma (RCC) cells. Validation of large-scale functional genomic screens confirms that PAX8 silencing leads to decreased proliferation of RCC cell lines. Epigenomic analyses of PAX8-dependent cistrome demonstrate that PAX8 largely occupies active enhancer elements controlling genes involved in various metabolic pathways. We selected the ferroxidase Ceruloplasmin (CP) as an exemplary gene to dissect PAX8 molecular functions. PAX8 recruits histone acetylation activity at bound enhancers looping onto the CP promoter. Importantly, CP expression correlates with sensitivity to PAX8 silencing and identifies a subset of RCC cases with poor survival. Our data identifies PAX8 as a candidate oncogene in RCC and provides a potential biomarker to monitor its activity. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000481750400001 |
WOS关键词 | TRANSCRIPTION FACTORS ; CANCER ; EXPRESSION ; MECHANISMS ; EVEROLIMUS ; CIRCUITRY ; IDENTITY ; ACCESS ; GROWTH |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203417 |
专题 | 资源环境科学 |
作者单位 | 1.Novartis Inst Biomed Res, Dis Area Oncol, Basel, Switzerland; 2.Novartis Inst Biomed Res, Chem Biol & Therapeut, Basel, Switzerland; 3.Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA; 4.Novartis Inst Biomed Res, Cambridge, MA USA; 5.Friedrich Miescher Inst Biomed Res, Basel, Switzerland; 6.Univ Basel, Basel, Switzerland; 7.German Canc Res Ctr, Div Stem Cells & Canc, Heidelberg, Germany; 8.Prinses Maxima Ctr Pediat Oncol, Utrecht, Netherlands; 9.Childrens Hosp Boston, Stem Cell Program, Boston, MA USA; 10.Harvard Med Sch, Dept Genet, Boston, MA 02115 USA; 11.Novartis Inst BioMed Res, Autoimmun Transplantat & Inflammat, Basel, Switzerland |
推荐引用方式 GB/T 7714 | Bleu, Melusine,Gaulis, Swann,Lopes, Rui,et al. PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Bleu, Melusine.,Gaulis, Swann.,Lopes, Rui.,Sprouffske, Kathleen.,Apfel, Verena.,...&Galli, Giorgio G..(2019).PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma.NATURE COMMUNICATIONS,10. |
MLA | Bleu, Melusine,et al."PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma".NATURE COMMUNICATIONS 10(2019). |
条目包含的文件 | 条目无相关文件。 |
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