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- Title
p21<sup>WAF1</sup> gene promoter is epigenetically silenced by CTIP2 and SUV39H1.
- Authors
Cherrier, T.; Suzanne, S.; Redel, L.; Calao, M.; Marban, C.; Samah, B.; Mukerjee, R.; Schwartz, C.; Gras, G.; Sawaya, B. E.; Zeichner, S. L.; Aunis, D.; Van Lint, C.; Rohr, O.
- Abstract
Mainly regulated at the transcriptional level, the cellular cyclin-dependent kinase inhibitor, CDKN1A/p21WAF1 (p21), is a major cell cycle regulator of the response to DNA damage, senescence and tumor suppression. Here, we report that COUP-TF-interacting protein 2 (CTIP2), recruited to the p21 gene promoter, silenced p21 gene transcription through interactions with histone deacetylases and methyltransferases. Importantly, treatment with the specific SUV39H1 inhibitor, chaetocin, repressed histone H3 lysine 9 trimethylation at the p21 gene promoter, stimulated p21 gene expression and induced cell cycle arrest. In addition, CTIP2 and SUV39H1 were recruited to the silenced p21 gene promoter to cooperatively inhibit p21 gene transcription. Induction of p21WAF1 gene upon human immunodeficiency virus 1 (HIV-1) infection benefits viral expression in macrophages. Here, we report that CTIP2 further abolishes Vpr-mediated stimulation of p21, thereby indirectly contributing to HIV-1 latency. Altogether, our results suggest that CTIP2 is a constitutive p21 gene suppressor that cooperates with SUV39H1 and histone methylation to silence the p21 gene transcription.
- Subjects
DNA damage; CELL cycle; PROTEIN kinases; METHYLTRANSFERASES; HIV; HIV infections; GENETIC regulation
- Publication
Oncogene, 2009, Vol 28, Issue 38, p3380
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2009.193