YEATS2 O-GlcNAcylation promotes chromatin association of the ATAC complex and lung cancer tumorigenesis.

ABSTRACT: The intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification is known to be enriched in the nucleus and on chromatin, but many of its chromatin targets remain to be identified. Herein, we demonstrate the O-GlcNAcylation of Yaf9, ENL, AF9, Taf14, Sas5 (YEATS) domain-containing 2 (YEATS2), a subunit of the chromatin Ada-two-A-containing (ATAC) complex and a reader of H3K27 acetylation levels. We show that YEATS2 interacts with the O-GlcNAc transferase and further pinpoint its major O-GlcNAcylation site to be Thr604 using electron transfer dissociation mass spectrometry. O-GlcNAcylation promotes the chromatin association of YEATS2, and the affinity between YEATS2 and other ATAC components on chromatin, such as ZZZ3, GCN5, and PCAF. Downstream, YEATS2-T604A mutants attenuated the A

SUBMITTER: Zhao J 

PROVIDER: S-EPMC12275198 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature