Activation-induced cytidine deaminase alters the subcellular localization of Tet family proteins

Yuko Arioka; Akira Watanabe; Kuniaki Saito; Yasuhiro Yamada

doi:10.1371/journal.pone.0045031

Activation-induced cytidine deaminase alters the subcellular localization of Tet family proteins

PLoS One. 2012;7(9):e45031. doi: 10.1371/journal.pone.0045031. Epub 2012 Sep 17.

Authors

Yuko Arioka¹, Akira Watanabe, Kuniaki Saito, Yasuhiro Yamada

Affiliation

¹ Department of Reprogramming Science, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.

Abstract

Activation-induced cytidine deminase (Aid), a unique enzyme that deaminates cytosine in DNA, shuttles between the nucleus and the cytoplasm. A recent study proposed a novel function of Aid in active DNA demethylation via deamination of 5-hydroxymethylcytosine, which is converted from 5-methylcytosine by the Ten-eleven translocation (Tet) family of enzymes. In this study, we examined the effect of simultaneous expression of Aid and Tet family proteins on the subcellular localization of each protein. We found that overexpressed Aid is mainly localized in the cytoplasm, whereas Tet1 and Tet2 are localized in the nucleus, and Tet3 is localized in both the cytoplasm and the nucleus. However, nuclear Tet proteins were gradually translocated to the cytoplasm when co-expressed with Aid. We also show that Aid-mediated translocation of Tet proteins is associated with Aid shuttling. Here we propose a possible role for Aid as a regulator of the subcellular localization of Tet family proteins.

Publication types

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

MeSH terms

Animals
Catalytic Domain
Cell Nucleus / enzymology
Cytidine Deaminase / metabolism*
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / metabolism
Dioxygenases / chemistry
Dioxygenases / metabolism*
HEK293 Cells
Humans
Mice
Multigene Family*
Protein Binding
Protein Transport
Proto-Oncogene Proteins / chemistry
Proto-Oncogene Proteins / metabolism
Subcellular Fractions / metabolism

Substances

DNA-Binding Proteins
Proto-Oncogene Proteins
TET1 protein, mouse
Dioxygenases
Tet2 protein, mouse
Tet3 protein, mouse
AICDA (activation-induced cytidine deaminase)
Cytidine Deaminase

Grants and funding

This work was supported by Grants-in-Aid from the Ministry of Health, Labour and Welfare of Japan, by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 23130508 and 24390096), and Grant from the Naito Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.