p21(WAF1) gene promoter is epigenetically silenced by CTIP2 and SUV39H1.

Cell Cycle; Cell Line; Cyclin-Dependent Kinase Inhibitor p21/genetics; Epigenesis, Genetic; Gene Expression Regulation; Gene Silencing; HIV-1/physiology; Humans; Macrophages/virology; Methyltransferases/physiology; Microglia/virology; Promoter Regions, Genetic; Repressor Proteins/physiology; Tumor Suppressor Proteins/physiology; Virus Replication; vpr Gene Products, Human Immunodeficiency Virus/physiology

Abstract :

[en] 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.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Cherrier, Thomas ; Université de Liège - ULiège > GIGA-Research

Suzanne, S.

Redel, L.

Calao, M.

Marban, C.

Samah, B.

Mukerjee, R.

Gras, G.

Sawaya, B. E.

Zeichner, S. L.

More authors (4 more)

Language :

English

Title :

p21(WAF1) gene promoter is epigenetically silenced by CTIP2 and SUV39H1.

Publication date :

2009

Journal title :

Oncogene

ISSN :

0950-9232

eISSN :

1476-5594

Publisher :

Nature Publishing Group, United Kingdom

Volume :

Issue :

Pages :

3380-9

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 25 January 2013

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