Open Accessp21WAF1 gene promoter is epigenetically silenced by CTIP2 and SUV39H1
Author(s) -
Thomas Cherrier,
Stella Suzanne,
Laetitia Redel,
Miriam Calao,
Céline Marban,
Boubekeur Samah,
Ruma Mukerjee,
Christian Schwartz,
Gabriel Gras,
Bassel E. Sawaya,
Steven L. Zeichner,
Dominique Aunis,
Carine Van Lint,
Olivier Rohr
Publication year - 2009
Publication title -
oncogene
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.395
H-Index - 342
eISSN - 1476-5594
pISSN - 0950-9232
DOI - 10.1038/onc.2009.193
Subject(s) - biology , dna methylation , regulation of gene expression , histone h3 , epigenetics , histone , gene expression , microbiology and biotechnology , gene , cancer research , genetics
Mainly regulated at the transcriptional level, the cellular cyclin-dependent kinase inhibitor, CDKN1A/p21(WAF1) (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 p21(WAF1) 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.