TET-mediated oxidation of methylcytosine causes TDG or NEIL glycosylase dependent gene reactivation.

ABSTRACT: The discovery of hydroxymethyl-, formyl- and carboxylcytosine, generated through oxidation of methylcytosine by TET dioxygenases, raised the question how these modifications contribute to epigenetic regulation. As they are subjected to complex regulation in vivo, we dissected links to gene expression with in vitro modified reporter constructs. We used an Oct4 promoter-driven reporter gene and demonstrated that in vitro methylation causes gene silencing while subsequent oxidation with purified catalytic domain of TET1 leads to gene reactivation. To identify proteins involved in this pathway we screened for TET interacting factors and identified TDG, PARP1, XRCC1 and LIG3 that are involved in base-excision repair. Knockout and rescue experiments demonstrated that gene reactivation depended o

SUBMITTER: Muller U 

PROVIDER: S-EPMC4117777 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature