LincRNA-p21 Activates p21 In cis to Promote Polycomb Target Gene Expression and to Enforce the G1/S Checkpoint
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Jacks_LincRNA.pdf
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Author(s)
Sarma, Kavitha
Lee, Jeannie T.
Dimitrova, Nadya
Zamudio, Jesse Ray
Jong, Robyn
Soukup, Dylan S.
Resnick, Rebecca
Whipple, Amanda Joy
Raj, Arjun
Sharp, Phillip A.
Date Issued
May 2014
Journal
Molecular Cell
Publisher
Elsevier
Citation
Dimitrova, Nadya, Jesse R. Zamudio, Robyn M. Jong, Dylan Soukup, Rebecca Resnick, Kavitha Sarma, Amanda J. Ward, et al. “LincRNA-P21 Activates P21 In Cis to Promote Polycomb Target Gene Expression and to Enforce the G1/S Checkpoint.” Molecular Cell 54, no. 5 (June 2014): 777–790.
Version
Author's final manuscript
Abstract
The p53-regulated long noncoding RNA lincRNA-p21 has been proposed to act in trans via several mechanisms ranging from repressing genes in the p53 transcriptional network to regulating mRNA translation and protein stability. To further examine lincRNA-p21 function, we generated a conditional knockout mouse model. We find that lincRNA-p21 predominantly functions in cis to activate expression of its neighboring gene, p21. Mechanistically, we show that lincRNA-p21 acts in concert with hnRNP-K as a coactivator for p53-dependent p21 transcription. Additional phenotypes of lincRNA-p21 deficiency could be attributed to diminished p21 levels, including deregulated expression and altered chromatin state of some Polycomb target genes, a defective G1/S checkpoint, increased proliferation rates, and enhanced reprogramming efficiency. These findings indicate that lincRNA-p21 affects global gene expression and influences the p53 tumor suppressor pathway by acting in cis as a locus-restricted coactivator for p53-mediated p21 expression.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.molcel.2014.04.025
