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| Status |
Public on Feb 08, 2019 |
| Title |
UBR7 is a novel E3 ubiquitin ligase for H2BK120 and acts as a tumor-suppressor in breast cancer [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Plant Homeo Domain (PHD) is a versatile chromatin reader/effector module which recognizes methylated, acetylated or unmodified histone substrates and regulates cellular gene expression programs. Although PHD domains shows selective epigenetic recognition of methylated, acetylated and unmodified histone substrates, there has been no previous report on its catalytic function regulating malignant transformation of cells. Here we report that PHD finger of UBR7 (Ubiquitin Protein Ligase E3 Component N-Recognin 7 (Putative)), in isolation or in context of full length protein, harbors E3 ubiquitin ligase activity towards monoubiquitination of histone H2B at lysine 120 . Knockdown of UBR7 in MCF10a and breast cancer cells decreased H2BK120ub both at the global levels and on specific genes. Conversely, overexpression of wild type, but not catalytic mutant, rescued H2BK120ub levels. Low UBR7 expression was associated with basal-like and triple negative breast cancers as well as showed poor expression in metastatic tumors. Consistently, UBR7 loss resulted in invasion properties, induced epithelial-to-mesenchymal transition and promoted metastasis. Conversely, ectopic expression of UBR7 reduced cell growth, invasion and tumor growth in mouse fat pad. Mechanistically, UBR7 reduced H2BK120ub gene body of cell-adhesion related genes as well as gene expression including on CDH4 gene. Importantly, rebuilding CDH4 levels rescued invasion phenotypes seen in UBR7-low cells. Collectively, our results establish that UBR7 PHD has novel H2B ubiquitin ligase activity and it suppresses tumor growth in basal-like breast cancers.
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| |
|
| Overall design |
Triplicate total RNA profiles in Wild Type and UBR7-shRNA MCF10A Cell Line
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| |
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| Contributor(s) |
Rai K, Terranova C |
| Citation(s) |
30923315 |
| |
| Submission date |
Jan 18, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Kunal Rai |
| E-mail(s) |
[email protected]
|
| Phone |
713-792-6809
|
| Organization name |
MD Anderson Cancer Center
|
| Department |
Genomic Medicine
|
| Lab |
Rai Lab
|
| Street address |
1801 East Rd
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77054 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (6)
|
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| This SubSeries is part of SuperSeries: |
| GSE93759 |
UBR7 is a novel E3 ubiquitin ligase for H2BK120 and acts as a tumor-suppressor in breast cancer |
|
| Relations |
| BioProject |
PRJNA362305 |
| SRA |
SRP096948 |
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