Histone　H2B　O-GlcNAcylation　is　an　important　post-translational　modification　of　chromatin　during　gene　transcription.　However,　how　this　epigenetic　modification　is　regulated　remains　unclear.　Here　we　found　that　the　energy-sensing　adenosine-monophosphate-activated　protein　kinase　(AMPK)　could　suppress　histone　H2B　O-GlcNAcylation.　AMPK　directly　phosphorylates　O-linked　beta-N-acetylglucosamine　(O-GlcNAc)　transferase　(OGT).　Although　this　phosphorylation　does　not　regulate　the　enzymatic　activity　of　OGT,　it　inhibits　OGT-chromatin　association,　histone　O-GlcNAcylation　and　gene　transcription.　Conversely,　OGT　also　O-GlcNAcylates　AMPK　and　positively　regulates　AMPK　activity,　creating　a　feedback　loop.　Taken　together,　these　results　reveal　a　crosstalk　between　the　LKB1-AMPK　and　the　hexosamine　biosynthesis　(HBP)-OGT　pathways,　which　coordinate　together　for　the　sensing　of　nutrient　state　and　regulation　of　gene　transcription.