O-GlcNAc regulates pluripotency and reprogramming by directly acting on core components of the pluripotency network

Cited 215 time in scopus
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Title
O-GlcNAc regulates pluripotency and reprogramming by directly acting on core components of the pluripotency network
Author(s)
H Jang; T W Kim; S Yoon; S Y Choi; T W Kang; Seon-Young Kim; Y W Kwon; E J Cho; H D Youn
Bibliographic Citation
Cell Stem Cell, vol. 11, no. 7, pp. 62-74
Publication Year
2012
Abstract
O-linked-N-acetylglucosamine (O-GlcNAc) has emerged as a critical regulator of diverse cellular processes, but its role in embryonic stem cells (ESCs) and pluripotency has not been investigated. Here we show that O-GlcNAcylation directly regulates core components of the pluripotency network. Blocking O-GlcNAcylation disrupts ESC self-renewal and reprogramming of somatic cells to induced pluripotent stem cells. The core reprogramming factors Oct4 and Sox2 are O-GlcNAcylated in ESCs, but the O-GlcNAc modification is rapidly removed upon differentiation. O-GlcNAc modification of threonine 228 in Oct4 regulates Oct4 transcriptional activity and is important for inducing many pluripotency-related genes, including Klf2, Klf5, Nr5a2, Tbx3, and Tcl1. A T228A point mutation that eliminates this O-GlcNAc modification reduces the capacity of Oct4 to maintain ESC self-renewal and reprogram somatic cells. Overall, our study makes a direct connection between O-GlcNAcylation of key regulatory transcription factors and the activity of the pluripotency network.
ISSN
1934-5909
Publisher
Elsevier-Cell Press
DOI
http://dx.doi.org/10.1016/j.stem.2012.03.001
Type
Article
Appears in Collections:
Korea Bioinformation Center > 1. Journal Articles
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