The ubiquitin ligase TRIM37 controls cancer-specific vulnerability to PLK4 inhibition
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA623614 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11505200.fastq.gz | Fastqsanger.gz | |||
| SRR11505201.fastq.gz | Fastqsanger.gz | |||
| SRR11505202.fastq.gz | Fastqsanger.gz | |||
| SRR11505203.fastq.gz | Fastqsanger.gz | |||
| SRR11505204.fastq.gz | Fastqsanger.gz |
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Project description: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. Identification of TRIM37 Binding targets in MCF7 cells from the two replicate experiments
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Project description: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.
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Project description:TRIM37 is a histone H2A ubiquitin ligase importantin breast cancer oncogenesis. To assess the neoplastic transformationsof normal breast epithelial cells in the context of TRIM37, we increased its expression and compared the gene expression network regulated by TRIM37 in control and TRIM37 overexpression.
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