RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells

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RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells
Title:
RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells
Journal Title:
Stem Cell Research
Keywords:
Publication Date:
01 July 2015
Citation:
Julien Jean Pierre Maury, Chadi A. EL Farran, Daniel Ng, Yuin-Han Loh, Xuezhi Bi, Muriel Bardor, Andre Boon-Hwa Choo, RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells, Stem Cell Research, Volume 15, Issue 1, July 2015, Pages 182-189, ISSN 1873-5061, http://dx.doi.org/10.1016/j.scr.2015.06.007.
Abstract:
O-linked-N-acetylglucosamine (O-GlcNAc) post-translationally modifies and regulates thousands of proteins involved in various cellular mechanisms. Recently, O-GlcNAc has been linked to human embryonic stem cells (hESC) differentiation, however the identity and function of O-GlcNAc proteins regulating hESC remain unknown. Here, we firstly identified O-GlcNAc modified human stem cell regulators such as hnRNP K, HP1γ, and especially RING1B/RNF2. Thereafter, we focused our work on RING1B which is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation. By point-mutation, we show that T250/S251 and S278 RING1B residues are bearing O-GlcNAc, and that T250/S251 O-GlcNAcylation decreases during differentiation. O-GlcNAc seems to regulate RING1B-DNA binding as suggested by our ChIP-sequencing results. Non-O-GlcNAcylated RING1B is found to be enriched near cell cycle genes whereas O-GlcNAcylated RING1B seems preferentially enriched near neuronal genes. Our data suggest that during hESC differentiation, the decrease of RING1B O-GlcNAcylation might enable PRC1 to switch its target to induce neuron differentiation. Overall, we demonstrate that O-GlcNAc modifies and regulates an essential epigenetic tool, RING1B, which may contribute to hESC pluripotency maintenance and differentiation.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
This research / project is supported by the BMRC-EDB, A*STAR, under its Industry Alignment Fund (IAF) Category 3 Platform (IAF311005A)
Description:
ISSN:
1873-5061
1876-7753
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