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Series GSE101987 Query DataSets for GSE101987
Status Public on Jul 05, 2018
Title BAP1 links epigenetic regulation of ferroptosis to tumor suppression
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Compared to the well-established roles of apoptosis in tumor suppression, the roles and regulatory mechanisms of ferroptosis, a non-apoptotic form of cell death, in tumor biology remain much less understood. BRCA1-associated protein 1 (BAP1) encodes a nuclear de-ubiquitinating (DUB) enzyme to reduce histone 2A ubiquitination (H2Aub) on chromatin, and is a tumor suppressor in several human cancers. Here, integrated transcriptomic, epigenomic, and cancer genomic analyses link BAP1 to metabolism-related biological processes, including oxidative stress response, and identify cystine transporter SLC7A11 as a BAP1-repressed target gene with high relevance to BAP1-mediated tumor suppression in human cancers. Functional studies reveal that BAP1, in a DUB-dependent manner, decreases H2Aub occupancy on the SLC7A11 promoter and represses SLC7A11 expression, and that BAP1 inhibits cystine uptake and promotes ferroptosis through repressing SLC7A11 expression. Finally, we show that BAP1 inhibits tumor development partly through SLC7A11, and that cancer-associated BAP1 mutants lose their abilities to repress SLC7A11 and to promote ferroptosis. Together, the results of our study show that BAP1 executes its tumor suppression function at least partly through its regulation of SLC7A11 and ferroptosis, and uncover a previously unappreciated mechanism coupling ferroptosis to tumor suppression.
Overall design ChIP-seq of H2AK119ub was applied in UMRC6 EV, BAP1 WT and C91A cells
Contributor(s) Shi J, Zhang Y, Gan B
Citation(s) 30202049
Submission date Jul 27, 2017
Last update date May 15, 2019
Contact name Jiejun Shi
Organization name Baylor College of Medicine
Department Molecular and Cellular Biology
Lab Li lab
Street address 1 Baylor Plaza
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (6)
GSM2720113 C91A_H2Aub_ChIP
GSM2720114 C91A_Input
GSM2720115 EV_H2Aub_ChIP
BioProject PRJNA396084
SRA SRP113743

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Supplementary file Size Download File type/resource
GSE101987_RAW.tar 1.3 Gb (http)(custom) TAR (of BW)
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Raw data are available in SRA
Processed data provided as supplementary file

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