Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

YEATS4 Reads Histone Crotonylation to Promote Fatty Acid Metabolism and Cancer Cell Stemness [CUT&Tag]

ABSTRACT: How histone lysine crotonylation (Kcr) is read and interpreted remains to be elucidated. We report here that YEATS4, a potential breast cancer driver identified recently by two independent genome-wide association studies, is a reader of H3K14cr. Integrative metabolomic, epigenomic, and transcriptomic analyses reveal that H3K14cr reading by YEATS4 is associated with a shift of cellular metabolic profile and transcription activation of a cohort of genes, including CD36, CPT1A, and ACOX1, that are critically involved in the uptake and metabolism of fatty acids. High expression of YEATS4 fortifies fatty acid metabolism, enhances self-renewal and growth of ALDH+ breast cancer stem cells, and is correlated with poor prognosis of breast cancer patients, especially the ER+ subtype. Our work uncovers YEATS4 as an “amplifier” in the feedforward circuit of histone crotonylation and lipid metabolism underlying the stemness and cell proliferation, supporting the pursuit of YEATS4 as a potential target for breast cancer intervention.

ORGANISM(S): Homo sapiens

PROVIDER: GSE256112 | GEO | 2025/09/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

YEATS4 Reads Histone Crotonylation to Promote Fatty Acid Metabolism and Cancer Cell Stemness [RNA-seq]

Project description:How histone lysine crotonylation (Kcr) is read and interpreted remains to be elucidated. We report here that YEATS4, a potential breast cancer driver identified recently by two independent genome-wide association studies, is a reader of H3K14cr. Integrative metabolomic, epigenomic, and transcriptomic analyses reveal that H3K14cr reading by YEATS4 is associated with a shift of cellular metabolic profile and transcription activation of a cohort of genes, including CD36, CPT1A, and ACOX1, that are critically involved in the uptake and metabolism of fatty acids. High expression of YEATS4 fortifies fatty acid metabolism, enhances self-renewal and growth of ALDH+ breast cancer stem cells, and is correlated with poor prognosis of breast cancer patients, especially the ER+ subtype. Our work uncovers YEATS4 as an “amplifier” in the feedforward circuit of histone crotonylation and lipid metabolism underlying the stemness and cell proliferation, supporting the pursuit of YEATS4 as a potential target for breast cancer intervention.

2025-09-14 | GSE256110 | GEO

YEATS4 Links Histone Crotonylation to Fatty-acid Uptake/Metabolism and Breast Cancer Stemness

Project 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.

2024-03-01 | PXD050262 |

Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification

Project description:We report the identification of 67 previously undescribed histone modifications, increasing the current number of known histone marks by about 70%. We further investigated one of the marks, lysine crotonylation (Kcr), confirming that it represents an evolutionarily-conserved histone posttranslational modification. The unique structure and genomic localization of histone Kcr suggest that it is mechanistically and functionally different from histone lysine acetylation (Kac). Specifically, in both human somatic and mouse male germ cell genomes, histone Kcr marks either active promoters or potential enhancers. In male germinal cells immediately following meiosis, Kcr is enriched on sex chromosomes and specifically marks testis-specific genes, including a significant proportion of X-linked genes that escape sex chromosome inactivation in haploid cells. These results therefore dramatically extend the repertoire of histone PTM sites and designate Kcr as a specific mark of active sex chromosome-linked genes in postmeiotic male germ cells. 2 histone marks (pan-lysine acetylation and pan-lysine crotonylation) were studied in 1 human cell type and 2 mouse cell types using ChIP-Seq. Input was sequenced for each cell type as a control. Pan-anti_Kac and pan-anti_Kcr antibodies were custom developed with PTM BioLab, Co., Ltd (Chicago, IL).

2011-10-06 | E-GEOD-32663 | biostudies-arrayexpress

Genome-wide profiling of histone lysine crotonylation reveals positive regulation of transcription in rice

Project description:Histone lysine crotonylation (Kcr) is a newly discovered post-translational modification (PTM) existing in mammalian. To assess relevance in histone Kcr and genome, we performed on genomic localization analysis of histone Kcr by ChIP-seq analysis.

2018-06-01 | GSE108542 | GEO

YEATS4 Reads Histone Crotonylation to Promote Fatty Acid Metabolism and Cancer Cell Stemness [RNA-seq]

Project description:YEATS4 Reads Histone Crotonylation to Promote Fatty Acid Metabolism and Cancer Cell Stemness [RNA-seq]

| PRJNA1078283 | ENA

YEATS4 Reads Histone Crotonylation to Promote Fatty Acid Metabolism and Cancer Cell Stemness [CUT&Tag]

Project description:YEATS4 Reads Histone Crotonylation to Promote Fatty Acid Metabolism and Cancer Cell Stemness [CUT&Tag]

| PRJNA1078281 | ENA

The Role of CDYL-Regulated Crotonylation of RPA1 in Homologous Recombination-Mediated DNA Repair

Project description:Lysine crotonylation (Kcr) is a recently-identified protein short-chain acylation. We have previously reported that chromodomain Y-like transcription corepressor CDYL acts as a crotonyl-CoA hydratase and negatively regulates histone Kcr. However, the global crotonylome of CDYL-regulated Kcr on non-histone substrates remains unclear. Using proteome-wide quantitative Kcr analysis, we identified 14,311 Kcr sites across 3,734 proteins in HeLa cells, providing by far the largest crotonylome data set from a single study. Upon depletion of CDYL, 1,141 Kcr sites from 759 proteins were increased by more than 1.5 fold, and 933 Kcr sites from 528 proteins were decreased by more than 0.67 fold. Upregulated crotonylome alterations upon CDYL depletion include components from diverse cellular pathways such as RNA splicing, DNA replication, and amino acid metabolism. Specifically, CDYL regulates K88 and K379 of crotonylation on RPA1, which affects its binding to other DNA repair factors including BLM, DNA2L, RAD50 and WRN. We showed evidence that CDYL-mediated RPA1 crotonylation is critical for the homologous recombination (HR) repair of camptothecin (CPT)-induced DNA damage. Together, our results provide a broad lysine crotonylome in response to CDYL and shed new light on the role of RPA1 Kcr in DNA repair, implicating functional importance of Kcr on non-histone substrates in diverse cellular processes.

2020-04-02 | PXD013616 | Pride

Large-Scale Analysis of Protein Crotonylation Reveals Its Diverse Functions in Pinellia ternate

Project description:We generated a global crotonylome analysis of the leaves in Pinellia ternata. We found 4509 crotonylated sites on 1757 proteins totally, and three specific amino acids surrounding crotonylation sites were identified in Pinellia ternata: KcrF, K***Y**Kcr and Kcr****R. Gene Ontology (GO) and KEGG pathway enrichment analyses showed that two crucial alkaloid biosynthesis related enzymes and many stress-related proteins were also highly crotonylated. Furthermore, several enzymes participate in the carbohydrate metabolism pathway, were modified also by lysine crotonylation.

2022-07-31 | PXD033142 | Pride

Large-Scale Analysis of Protein Crotonylation Reveals Its Diverse Functions in Pinellia ternate

2022-04-13 | PXD033154 | Pride

Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification

2011-10-06 | GSE32663 | GEO