PXD060970-1

PXD060970 is an original dataset announced via ProteomeXchange.

Title	YEATS2 O-GlcNAcylation Promotes Chromatin Association of the ATAC complex and Lung Cancer Tumorigenesis
Description	The intracellular O-linked N-acetylglucosamine (O-GlcNAc) modification is known to be enriched in the nucleus and in particular on chromatin, but many of its chromatin targets remain to be identified. Herein we demonstrate the O-GlcNAcylation of YEATS Domain Containing 2 (YEATS2), a subunit of the chromatin Ada-two-A-containing (ATAC) complex and a reader of histone H3K27ac. We show that YEATS2 interacts with the O-GlcNAc transferase (OGT) 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 attenuated the ATAC-dependent histone H3K9ac levels and inactivated the expression of essential ribosomal genes as shown in chromatin immunoprecipitation assays. Further, xenograft experiments show that YEATS2 O-GlcNAcylation promotes lung cancer tumorigenesis. Our work reveals the critical role of YEATS2 O-GlcNAcylation in stabilizing the ATAC complex on chromatin and expands the chromatin substrates of OGT.
HostingRepository	PRIDE
AnnounceDate	2025-07-28
AnnouncementXML	Submission_2025-07-27_16:04:18.352.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD060970
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Wen Zhou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-19 09:40:04	ID requested
⏵ 1	2025-07-27 16:04:19	announced

10.6019/PXD060970;

10.1016/j.jbc.2025.110388;

Zhao J, Zhao Z, Zhou W, Zhang J, Chen J, Sun J, Li J, YEATS2 O-GlcNAcylation promotes chromatin association of the ATAC complex and lung cancer tumorigenesis. J Biol Chem, 301(7):110388(2025) [pubmed]

submitter keyword: O-GlcNAc

YEATS2

ATAC

H3K9ac

ZZZ3

Wen Zhou
contact affiliation	Peking University
contact email	wen.zhou@pku.edu.cn
lab head
Wen Zhou
contact affiliation	Peking University
contact email	wen.zhou@pku.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060970
     1. Label: PRIDE project
     2. Name: YEATS2 O-GlcNAcylation Promotes Chromatin Association of the ATAC complex and Lung Cancer Tumorigenesis