Journal article

TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS

R Deplus, B Delatte, MK Schwinn, M Defrance, J Méndez, N Murphy, MA Dawson, M Volkmar, P Putmans, E Calonne, AH Shih, RL Levine, O Bernard, T Mercher, E Solary, M Urh, DL Daniels, F Fuks

EMBO Journal | NATURE PUBLISHING GROUP | Published : 2013

Abstract

TET proteins convert 5-methylcytosine to 5-hydroxymethylcytosine, an emerging dynamic epigenetic state of DNA that can influence transcription. Evidence has linked TET1 function to epigenetic repression complexes, yet mechanistic information, especially for the TET2 and TET3 proteins, remains limited. Here, we show a direct interaction of TET2 and TET3 with O-GlcNAc transferase (OGT). OGT does not appear to influence hmC activity, rather TET2 and TET3 promote OGT activity. TET2/3-OGT co-localize on chromatin at active promoters enriched for H3K4me3 and reduction of either TET2/3 or OGT activity results in a direct decrease in H3K4me3 and concomitant decreased transcription. Further, we show ..

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University of Melbourne Researchers

Grants

Awarded by National Cancer Institute


Funding Acknowledgements

RD, MD and MV were supported by the Belgian FNRS. FF is an FNRS 'Senior Research Associate'. BD is an 'FNRS Aspirant'. FF's laboratory was funded by grants from the FNRS and Televie, the 'Interuniversity Attraction Poles' (IAP Phase VII no P7/03) and by the 'Action de Recherche Concertee' (AUWB-2010-2015 ULB-No 7). MKS, JM, NM, MU, and DLD are supported by Promega Corporation. We wish to thank Kazusa DNA Research Institute for providing vectors, MSBioworks for all mass spectrometry analysis, Dr Martin Rosenberg for thoughtful advice and continued support, and Prof. David Jeruzalmi for critical reading of the manuscript.