PXD050262-1

PXD050262 is an original dataset announced via ProteomeXchange.

Title	YEATS4 Links Histone Crotonylation to Fatty-acid Uptake/Metabolism and Breast Cancer Stemness
Description	The integration between epigenetic regulation and metabolism is critical to maintain cellular homeostasis. As an epigenetic mark mainly linked to gene activation, histone crotonylation (Kcr) uses the donor of crotonyl-CoA, a metabolite generated primarily from fatty acid oxidation. Whether there is an intrinsic crosstalk between histone Kcr and fatty acid metabolism remains to be explored. We report here that YEATS family protein YEATS4 is a reader of histone Kcr preferentially towards H3K14cr. YEATS4 is amplified and overexpressed in breast cancer cells, mainly in the ER+ subtype. Integrative epigenomic and transcriptomic analyses reveals extensively overlapped chromatin distribution of YEATS4 with H3K14cr, leading to activation of multiple genes involved in fatty-acid trafficking and metabolism, such as CD36, CPT1/2, and ACOX1. Depletion of YEATS4 in breast cancer cells led to compromised fatty acid uptake and -oxidation. Interestingly, YEATS4 is upregulated in ALDH+ breast cancer stem cells, leading to boosted fatty acid metabolism, enhanced self-renewal, and accelerated tumor growth. Clinicalpathological evidence indicates that elevated YEATS4 expression is correlated with poor prognosis and worse overall survival of ER+ breast cancer patients. Together, our study uncovers a feedforward epigenetic-metabolic loop implicated in breast carcinogenesis, supporting the pursuit of YEATS4 as a potential therapeutic target for breast cancer intervention.
HostingRepository	iProX
AnnounceDate	2024-03-01
AnnouncementXML	Submission_2025-01-01_19:49:11.128.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zijun Peng
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-01 02:31:47	ID requested
⏵ 1	2025-01-01 19:49:11	announced

Dataset with its publication pending

submitter keyword: YEATS4, histone crotonylation, fatty acid metabolism, breast cancer stemness

Jing Liang
contact affiliation	Peking University
contact email	liang_jing@hsc.pku.edu.cn
lab head
Zijun Peng
contact affiliation	Peking University
contact email	zj_peng@126.com
dataset submitter

iProX dataset URI