@article{ad0b8dd1d4ea4168aa6062bfeae4ce7b,
title = "Cistrome analysis of YY1 uncovers a regulatory axis of YY1:BRD2/4-PFKP during tumorigenesis of advanced prostate cancer",
abstract = "Castration-resistant prostate cancer (CRPC) is a terminal disease and the molecular underpinnings of CRPC development need to be better understood in order to improve its treatment. Here, we report that a transcription factor Yin Yang 1 (YY1) is significantly overexpressed during prostate cancer progression. Functional and cistrome studies of YY1 uncover its roles in promoting prostate oncogenesis in vitro and in vivo, as well as sustaining tumor metabolism including the Warburg effect and mitochondria respiration. Additionally, our integrated genomics and interactome profiling in prostate tumor show that YY1 and bromodomain-containing proteins (BRD2/4) co-occupy a majority of gene-regulatory elements, coactivating downstream targets. Via gene loss-of-function and rescue studies and mutagenesis of YY1-bound cis-elements, we unveil an oncogenic pathway in which YY1 directly binds and activates PFKP, a gene encoding the rate-limiting enzyme for glycolysis, significantly contributing to the YY1-enforced Warburg effect and malignant growth. Altogether, this study supports a master regulator role for YY1 in prostate tumorigenesis and reveals a YY1:BRD2/4-PFKP axis operating in advanced prostate cancer with implications for therapy.",
author = "Chenxi Xu and Tsai, {Yi Hsuan} and Galbo, {Phillip M.} and Weida Gong and Storey, {Aaron J.} and Yuemei Xu and Byrum, {Stephanie D.} and Lingfan Xu and Whang, {Young E.} and Parker, {Joel S.} and MacKintosh, {Samuel G.} and Edmondson, {Ricky D.} and Tackett, {Alan J.} and Jiaoti Huang and Deyou Zheng and Earp, {H. Shelton} and Wang, {Gang Greg} and Ling Cai",
note = "Funding Information: University of Arkansas for Medical Sciences Proteomics Core Facility; IDeA National Resource for Proteomics; Translational Research Institute through the National Center for Advancing Translational Sciences of the National Institutes of Health; Center for Translational Pediatric Research Bioinformatics Core Resource [TL1TR003109, P20GM121293, P20GM103625, P20GM103429, S10OD018445, UL1TR003107, R01CA236209]; UCRF Stimulus Initiative Grant of UNC Lineberger Cancer Center (to L.C., in part); UNC Cancer Center are supported in part by the UNC Lineberger Comprehensive Cancer Center Core Support Grant [P30-CA016086]; G.G.W. is an American Cancer Society (ACS) Research Scholar and a Leukemia and Lymphoma Society (LLS) Scholar. Funding for open access charge: UCRF Stimulus Initiative Grant of UNC Lineberger Cancer Center (to L.C.). Conflict of interest statement. J.H. is a consultant for or owns shares in the following companies: Kingmed, More- Health, OptraScan, Genetron, Omnitura, Vetonco, York Biotechnology, Genecode and Sisu Pharma. G.G.W. is an inventor of a patent application filed by University of North Carolina at Chapel Hill. G.G.W. received research fund from the Deerfield Management/Pinnacle Hill Company. Publisher Copyright: {\textcopyright} 2021 The Author(s) 2021.",
year = "2021",
month = may,
day = "21",
doi = "10.1093/nar/gkab252",
language = "English (US)",
volume = "49",
pages = "4971--4988",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "9",
}
