RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells
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 regulatin...
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doaj-574ec3783a9c4bef94e9a5a4e94ff1512020-11-24T21:25:48ZengElsevierStem Cell Research1873-50611876-77532015-07-0115118218910.1016/j.scr.2015.06.007RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cellsJulien Jean Pierre Maury0Chadi A. EL Farran1Daniel Ng2Yuin-Han Loh3Xuezhi Bi4Muriel Bardor5Andre Boon-Hwa Choo6Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, 138668 SingaporeInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, #08-01 Proteos, 138673 SingaporeBioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, 138668 SingaporeInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, #08-01 Proteos, 138673 SingaporeBioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, 138668 SingaporeBioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, 138668 SingaporeBioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, 138668 SingaporeO-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.http://www.sciencedirect.com/science/article/pii/S187350611500080X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julien Jean Pierre Maury Chadi A. EL Farran Daniel Ng Yuin-Han Loh Xuezhi Bi Muriel Bardor Andre Boon-Hwa Choo |
spellingShingle |
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 |
author_facet |
Julien Jean Pierre Maury Chadi A. EL Farran Daniel Ng Yuin-Han Loh Xuezhi Bi Muriel Bardor Andre Boon-Hwa Choo |
author_sort |
Julien Jean Pierre Maury |
title |
RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells |
title_short |
RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells |
title_full |
RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells |
title_fullStr |
RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells |
title_full_unstemmed |
RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells |
title_sort |
ring1b o-glcnacylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells |
publisher |
Elsevier |
series |
Stem Cell Research |
issn |
1873-5061 1876-7753 |
publishDate |
2015-07-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S187350611500080X |
work_keys_str_mv |
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