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Genes Cancer. 2010 May;1(5):434-43. doi: 10.1177/1947601910373794.

Dnmt1/Transcription factor interactions: an alternative mechanism of DNA methylation inheritance.

Author information

1
Institut de Recherche Thérapeutique de l'Université de Nantes, INSERM U892, Centre de Recherche en Cancérologie Nantes-Angers, Equipe Aspect Mécanistiques et Physiopathologiques de l'Activité des Protéines de la Famille de Bcl-2, Equipe Labellisée Ligue Nationale Contre le Cancer, Nantes, France.

Abstract

DNA methylation inheritance is the process of copying, via the DNA methyltransferase 1 (Dnmt1), the pre-existing methylation patterns onto the new DNA strand during DNA replication. Experiments of chromatin immunoprecipitation, measurement of maintenance methyltransferase activity, proximity ligation in situ assays (P-LISA, Duolink/Olink), and transcription factor arrays demonstrate that Dnmt1 interacts with transcription factors to promote site-specific DNA methylation inheritance, while the Dnmt1-PCNA-UHRF1 complex promotes the DNA methylation inheritance without site preference. We also show that the Dnmt1-PCNA-UHRF1 and Dnmt1/transcription factor complexes methylate DNA by acting as a single player or in cooperation. Thus, our data establish that the copying of the pre-existing methylation pattern is governed by the orchestration of the untargeted and the targeted mechanisms of DNA methylation inheritance, which are themselves dictated by the partners of Dnmt1.

KEYWORDS:

DNA methylation; Dnmt; epigenetics

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