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Oncotarget. 2016 Sep 13;7(37):58939-58952. doi: 10.18632/oncotarget.10624.

The interplay between the lysine demethylase KDM1A and DNA methyltransferases in cancer cells is cell cycle dependent.

Author information

Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB-Cancer Research Centre (U-CRC), Université Libre de Bruxelles, 1070 Brussels, Belgium.
Centre de Recherche en Cancérologie Nantes-Angers, INSERM, U892, Equipe Apoptose et progression tumorale, BP7021, 44007 Nantes, France.
Département de Recherche en Cancérologie, Faculté de Médecine, Université de Nantes, IFR26, F-4400, Nantes, France.
LaBCT, Institut de Cancérologie de l'Ouest,44805 Nantes, Saint Herblain Cedex, France.


DNA methylation and histone modifications are key epigenetic regulators of gene expression, and tight connections are known between the two. DNA methyltransferases are upregulated in several tumors and aberrant DNA methylation profiles are a cancer hallmark. On the other hand, histone demethylases are upregulated in cancer cells. Previous work on ES cells has shown that the lysine demethylase KDM1A binds to DNMT1, thereby affecting DNA methylation. In cancer cells, the occurrence of this interaction has not been explored. Here we demonstrate in several tumor cell lines an interaction between KDM1A and both DNMT1 and DNMT3B. Intriguingly and in contrast to what is observed in ES cells, KDM1A depletion in cancer cells was found not to trigger any reduction in the DNMT1 or DNMT3B protein level or any change in DNA methylation. In the S-phase, furthermore, KDM1A and DNMT1 were found, to co-localize within the heterochromatin. Using P-LISA, we revealed substantially increased binding of KDM1A to DNMT1 during the S-phase. Together, our findings propose a mechanistic link between KDM1A and DNA methyltransferases in cancer cells and suggest that the KDM1A/DNMT1 interaction may play a role during replication. Our work also strengthens the idea that DNMTs can exert functions unrelated to act on DNA methylation.


DNA methylation; KDM1A; cancer; cell cycle; histone demethylation

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