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Status |
Public on Jun 03, 2021 |
Title |
Yin Yang 1 interacts with bromodomain-containing coactivators to promote tumorigenesis of advanced prostate cancer |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
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 treatments. 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, as well as 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 YY1-enforced Warburg effect and malignant growth. Altogether, this study supports a master regulator role for YY1 in prostate tumor and reveals a YY1:BRD2/4-PFKP axis operating in advanced prostate cancer with implications for therapy.
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Overall design |
Examination of the genome-wide binding of YY1 in LNCaP prostate cancer cells .
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Contributor(s) |
Xu C, Wang GG, Cai L |
Citation(s) |
33849067 |
Submission date |
Jan 12, 2021 |
Last update date |
Jun 03, 2021 |
Contact name |
Chenxi Xu |
E-mail(s) |
xuchenxi@email.unc.edu
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Phone |
9199034127
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Organization name |
University of North Carolina at Chapel Hill
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Department |
Lineberger Comprehensive Cancer Center
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Lab |
Greg Wang lab
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Street address |
450 West Drive, CB 7295, UNC cancer center, room 31-331 Chapel Hill, NC
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City |
Chapel Hill |
State/province |
North Carolina |
ZIP/Postal code |
27599 |
Country |
USA |
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Platforms (1) |
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Samples (4)
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This SubSeries is part of SuperSeries: |
GSE153640 |
A regulatory axis of YY1-PFKP promotes aggressive prostate tumorigenesis via potentiating tumor cell metabolism |
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Relations |
BioProject |
PRJNA691640 |
SRA |
SRP301490 |