HDAC1-mSin3a-NCOR1, Dnmt3b-HDAC1-Egr1 and Dnmt1-PCNA-UHRF1-G9a regulate the NY-ESO1 gene expression

Pierre-François Cartron; Christophe Blanquart; Eric Hervouet; Marc Gregoire; François M Vallette

doi:10.1016/j.molonc.2012.11.004

HDAC1-mSin3a-NCOR1, Dnmt3b-HDAC1-Egr1 and Dnmt1-PCNA-UHRF1-G9a regulate the NY-ESO1 gene expression

Mol Oncol. 2013 Jun;7(3):452-63. doi: 10.1016/j.molonc.2012.11.004. Epub 2012 Dec 21.

Authors

Pierre-François Cartron¹, Christophe Blanquart, Eric Hervouet, Marc Gregoire, François M Vallette

Affiliation

¹ Centre de Recherche en Cancérologie Nantes-Angers, INSERM U892, Equipe Apoptose et Progression Tumorale, Equipe labellisée Ligue Nationale Contre le Cancer, 8 Quai Moncousu, BP 7021, 44007 Nantes, France. pierre-francois.cartron@univ-nantes.fr

Abstract

The NY-ESO1 gene is a cancer/testis antigen considered to be suitable target for the immunotherapy of human malignancies. Despite the identification of the epigenetical silencing of the NY-ESO1 gene in a large variety of tumors, the molecular mechanism involved in this phenomenon is not fully elucidated. In two non epithelial cancers (glioma and mesothelioma), we found that the epigenetic regulation of the NY-ESO1 gene requires the sequential recruitment of the HDAC1-mSin3a-NCOR, Dnmt3b-HDAC1-Egr1 and Dnmt1-PCNA-UHRF1-G9a complexes. Thus, our data illustrate the orchestration of a sequential epigenetic mechanism including the histone deacetylation and methylation, and the DNA methylation processes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Neoplasm / genetics*
CCAAT-Enhancer-Binding Proteins / metabolism
Cell Line, Tumor
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases / metabolism
DNA Methylation
DNA Methyltransferase 3B
Early Growth Response Protein 1 / metabolism
Gene Expression Regulation, Neoplastic*
Gene Silencing*
Glioma / genetics*
Glioma / metabolism
Histocompatibility Antigens / metabolism
Histone Deacetylase 1 / metabolism
Histone-Lysine N-Methyltransferase / metabolism
Humans
Membrane Proteins / genetics*
Mesothelioma / genetics*
Mesothelioma / metabolism
Multiprotein Complexes / metabolism
Nuclear Receptor Co-Repressor 1 / metabolism
Proliferating Cell Nuclear Antigen / metabolism
Repressor Proteins / metabolism
Sin3 Histone Deacetylase and Corepressor Complex
Ubiquitin-Protein Ligases

Substances

Antigens, Neoplasm
CCAAT-Enhancer-Binding Proteins
CTAG1B protein, human
Early Growth Response Protein 1
Histocompatibility Antigens
Membrane Proteins
Multiprotein Complexes
NCOR1 protein, human
Nuclear Receptor Co-Repressor 1
Proliferating Cell Nuclear Antigen
Repressor Proteins
SIN3A transcription factor
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases
DNMT1 protein, human
EHMT2 protein, human
Histone-Lysine N-Methyltransferase
UHRF1 protein, human
Ubiquitin-Protein Ligases
HDAC1 protein, human
Histone Deacetylase 1
Sin3 Histone Deacetylase and Corepressor Complex