|
| Status |
Public on Oct 06, 2014 |
| Title |
TRIM37 is a novel H2A ubiquitin ligase and a Breast Cancer Oncogene |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
|
| Summary |
The TRIM37 gene is mutatedin Mulbery nanism, a rare autosomal recessive disorder, and is in the 17q23 chromosomal region that is amplified in up to ~40% of breast cancers. Trim37 contains a RING finger domain, a hallmark of E3 ubiquitin ligases, but the protein substrate(s) of Trim37 is unknown. Mono-ubiquitination of histone H2A is a chromatin modification associated with transcriptional repression and here we report that Trim37 is an H2A ubiquitin ligase. Genome-wide Chip-CHIP experiments indicate that in human breast cancer cells containing amplified 17q23, Trim37 is bound to the promoters of many tumor suppressor genes. RNA interference (RNAi)-mediated knockdown of Trim37 results in loss of ubiquitinated H2A, dissociation of PRC1 and PRC2, and transcriptional reactivation of silenced genes. Knockdown of Trim37 in human breast cancer cells containing amplified 17q23 substantially decreases tumor growth in mouse xenografts. Collectively, our results reveal Trim37 as a new H2A ubiquitin ligase that is overexpressed in a subset of breast cancers and redirects PRC2 to silence tumor suppressors and other genes resulting in oncogenesis.
|
| |
|
| Overall design |
Identification of TRIM37 Binding targets in MCF7 cells from the two replicate experiments
|
| |
|
| Contributor(s) |
Bhatnagar S, Green MR |
| Citation(s) |
25470042 |
| |
| Submission date |
Jun 21, 2013 |
| Last update date |
Jan 21, 2015 |
| Contact name |
Sanchita Bhatnagar |
| Organization name |
University of California Davis
|
| Department |
Medical Microbiology and Immunology
|
| Lab |
Sanchita Bhatnagar Lab
|
| Street address |
1275 Health Sciences, Tupper Hall 3134
|
| City |
Davis |
| State/province |
CA |
| ZIP/Postal code |
95616 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL5082 |
[Hs_PromPR] Affymetrix Human Promoter 1.0R Array |
|
| Samples (18)
|
|
| Relations |
| BioProject |
PRJNA209139 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE48196_H2A1mutGSE48196_quantileNormalized_log2_rep1.txt.gz |
131.5 Mb |
(ftp)(http) |
TXT |
| GSE48196_H2A2mutGSE48196_quantileNormalized_log2_rep2.txt.gz |
140.2 Mb |
(ftp)(http) |
TXT |
| GSE48196_H2AGSE48196_quantileNormalized_log2_rep1.txt.gz |
131.9 Mb |
(ftp)(http) |
TXT |
| GSE48196_H2AGSE48196_quantileNormalized_log2_rep2.txt.gz |
132.6 Mb |
(ftp)(http) |
TXT |
| GSE48196_H3K1c9GSE48196_quantileNormalized_log2_rep1.txt.gz |
142.1 Mb |
(ftp)(http) |
TXT |
| GSE48196_H3K27GSE48196_quantileNormalized_log2_rep2.txt.gz |
148.1 Mb |
(ftp)(http) |
TXT |
| GSE48196_H3K27GSE48196_quantileNormalized_log2_rep3.txt.gz |
146.5 Mb |
(ftp)(http) |
TXT |
| GSE48196_H3K2c9GSE48196_quantileNormalized_log2_rep2.txt.gz |
145.7 Mb |
(ftp)(http) |
TXT |
| GSE48196_RAW.tar |
317.3 Mb |
(http)(custom) |
TAR (of CEL) |
| GSE48196_quantileNormalized_log2_rep2_EZGSE48196_H2.txt.gz |
148.1 Mb |
(ftp)(http) |
TXT |
| GSE48196_quantileNormalized_log2_rep3_EZGSE48196_H2.txt.gz |
143.7 Mb |
(ftp)(http) |
TXT |
| Processed data are available on Series record |
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