O-GlcNAc regulates pluripotency and reprogramming by directly acting on core components of the pluripotency network.
Cell Stem Cell, 2012/7/06;11(1):62-74.
Jang H[1], Kim TW, Yoon S, Choi SY, Kang TW, Kim SY, Kwon YW, Cho EJ, Youn HD
Affiliations
PMID: 22608532DOI: 10.1016/j.stem.2012.03.001
Impact factor: 25.269
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.
MeSH terms
Acetylglucosamine; Amino Acid Sequence; Animals; Cell Differentiation; Cell Proliferation; Cellular Reprogramming; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Glycosylation; Humans; Mice; Mice, Inbred C57BL; Models, Biological; Molecular Sequence Data; Mutation; Octamer Transcription Factor-3; Pluripotent Stem Cells; SOXB1 Transcription Factors; Transcription, Genetic
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