SETD1A modulates cell cycle progression through a miRNA network that regulates p53 target genes

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Tajima, Ken
Javaid, Sarah
Tam, Oliver
Liu, Mingzhu
Engstrom, Amanda
Takahashi, Fumiyuki
Black, Joshua C.
Hammell, Molly
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ncomms9257Metadata
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Tajima, K., T. Yae, S. Javaid, O. Tam, V. Comaills, R. Morris, B. S. Wittner, et al. 2015. “SETD1A modulates cell cycle progression through a miRNA network that regulates p53 target genes.” Nature Communications 6 (1): 8257. doi:10.1038/ncomms9257. http://dx.doi.org/10.1038/ncomms9257.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667427/pdf/Terms of Use
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