Tajima, K., Yae, T., Javaid, S., Tam, O., Comaills, V., Morris, R., Wittner, B. S., Liu, M., Engstrom, A., Takahashi, F., Black, J. C., Ramaswamy, S., Shioda, T., Hammell, M., Haber, D. A., Whetstine, J. R., Maheswaran, S. (September 2015) SETD1A modulates cell cycle progression through a miRNA network that regulates p53 target genes. Nat Commun, 6. p. 8257. ISSN 2041-1723 (Electronic)2041-1723 (Linking)
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Abstract
Expression of the p53-inducible antiproliferative gene BTG2 is suppressed in many cancers in the absence of inactivating gene mutations, suggesting alternative mechanisms of silencing. Using a shRNA screen targeting 43 histone lysine methyltransferases (KMTs), we show that SETD1A suppresses BTG2 expression through its induction of several BTG2-targeting miRNAs. This indirect but highly specific mechanism, by which a chromatin regulator that mediates transcriptional activating marks can lead to the downregulation of a critical effector gene, is shared with multiple genes in the p53 pathway. Through such miRNA-dependent effects, SETD1A regulates cell cycle progression in vitro and modulates tumorigenesis in mouse xenograft models. Together, these observations help explain the remarkably specific genetic consequences associated with alterations in generic chromatin modulators in cancer.
| Item Type: | Paper |
|---|---|
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53 |
| CSHL Authors: | |
| Communities: | CSHL labs > Hammell M. lab CSHL Cancer Center Program > Cancer Genetics and Genomics Program |
| Depositing User: | Matt Covey |
| Date: | 23 September 2015 |
| Date Deposited: | 01 Oct 2015 21:42 |
| Last Modified: | 05 Nov 2020 19:17 |
| PMCID: | PMC4667427 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/31895 |
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