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

Julien Jean Pierre Maury (1, 2) , Chadi a El Farran (1, 2) , Daniel Ng (1) , Yuin-Han Loh (1, 2) , Xuezhi Bi (1) , Muriel Bardor (3, 1) , Andre Boon-Hwa Choo (1, 2)

1 A*STAR - Agency for science, technology and research [Singapore]
2 NUS - National University of Singapore
3 Glyco-MEV - Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale

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 T 250 /S 251 and S 278 RING1B residues are bearing O-GlcNAc, and that T 250 /S 251 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

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Julien Jean Pierre Maury, Chadi a El Farran, Daniel Ng, Yuin-Han Loh, Xuezhi Bi, et al.. RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells. Stem Cell Research, 2015, 15 (1), pp.182 - 189. ⟨10.1016/j.scr.2015.06.007⟩. ⟨hal-01841067⟩