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| Status |
Public on Jan 17, 2020 |
| Title |
A hypermethylation strategy utilized by enhancer-bound CARM1 to promote estrogen receptor a-dependent transcriptional activation and breast carcinogenesis (RNA-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
While protein arginine methyltransferases (PRMTs) and PRMT-catalyzed protein methylation have been well-known to be involved in a myriad of biological processes, their roles in carcinogenesis, particularly in estrogen receptor alpha (ERa)-positive breast cancers, remain incompletely understood. Here we focused on investigating PRMT4 (also called coactivator associated arginine methyltransferase 1, CARM1) due to its high expression and the associated poor prognosis in ERa-positive breast cancers. We first uncovered the chromatin-binding landscape and transcriptional targets of CARM1 in the presence of estrogen in ERa-positive breast cancer cells employing genomic and transcriptomics approaches. CARM1 was found to be predominantly and specifically recruited to ERa-bound active enhancers and essential for the transcriptional activation of cognate estrogen-induced gene transcriptional activation in response to estrogen. Global mapping of CARM1 substrates revealed that CARM1 methylates a large cohort of proteins with diverse biological functions, including regulation of intracellular estrogen receptor signaling, chromatin organization, chromatin remodeling and others. Intriguingly, a number of proteins were hypermethylated exclusively by CARM1 on a cluster of arginine residues. Exemplified by MED12, hypermethylation of these proteins by CARM1 served as a molecular beacon for recruiting coactivator protein, tudor domain-containing 3 (TDRD3), to ensure the full activation of estrogen/ERa target genes. In consistent with its critical role in estrogen-induced gene transcriptional activation, CARM1 was found to promote cell proliferation of ERa-positive breast cancer cells in vitro and tumor growth in mice. Taken together, our study uncovered a “hypermethylation” strategy utilized by CARM1 in gene transcriptional regulation, and suggested that CARM1 can server as a therapeutic target for breast cancer treatment.
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| Overall design |
RNA-seq performed in this study was designed to understand the molecular mechanisms underlying CARM1 regulation of breast cancer
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| |
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| Contributor(s) |
Liu W, Peng B, Ding J |
| Citation(s) |
32206101 |
| |
| Submission date |
Dec 27, 2018 |
| Last update date |
Mar 30, 2020 |
| Contact name |
Jiancheng Ding |
| E-mail(s) |
[email protected]
|
| Organization name |
Xiamen University
|
| Street address |
School of Pharmaceutical Sciences, Xiamen University Xiang`an South Road
|
| City |
Xiamen |
| State/province |
Fujian |
| ZIP/Postal code |
361102 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
|
| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE124449 |
A hypermethylation strategy utilized by enhancer-bound CARM1 to promote estrogen receptor a-dependent transcriptional activation and breast carcinogenesis |
|
| Relations |
| BioProject |
PRJNA512031 |
| SRA |
SRP174618 |
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