Histone crotonylation links metabolism with gene expression
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA491407 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7851530.fastq.gz | Fastqsanger.gz | |||
| SRR7851540.fastq.gz | Fastqsanger.gz | |||
| SRR7851521.fastq.gz | Fastqsanger.gz | |||
| SRR7851531.fastq.gz | Fastqsanger.gz | |||
| SRR7851541.fastq.gz | Fastqsanger.gz |
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Project description:We performed RNA-seq across the yeast metabolic cycle (YMC) in wild-type and a strain containing a point mutant in TAF14 (W81A) that abolishes binding to acylated histones. We also performed ChIPseq using antibodies directed against histone H3K9acetyl, histone H3K9crotonyl, histone H3 across the wild-type YMC.
2019-08-28 | GSE120019 | GEO
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 | GSE256112 | GEO
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
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 |
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
Project description:In this study we report that histone crotonylation promotes human embryonic stem cell differentiation to endoderm cells. Addition of crotonate, a precursor for crotonyl-CoA and therefore histone crotonylation, dramatically enhanced endoderm cell differentiation from human embryonic stem cells, while incubation of acetate, a precursor of acetyl-CoA and therefore histone acetylation, did not change the efficiency of endoderm differentiation.
2021-02-23 | GSE130341 | GEO
Project description:Histone lysine crotonylation is a non-acetyl histone lysine modification that is evolutionarily conserved. It plays an important role in regulating various biological processes, including gene transcriptional regulation, spermatogenesis, and cell cycle. However, the dynamic changes and functions of histone crotonylation in preimplantation embryonic development in mammals remain unclear. In this study, we have shown that the transcription coactivator P300 functions as a writer of histone crotonylation during embryonic development. Depletion of P300 resulted in significant developmental defects and dysregulation of the transcriptome of embryos. Importantly, we demonstrated that P300 catalyzes the crotonylation of histone, directly stimulating transcription and regulating gene expression, thereby ensuring successful embryo development to the blastocyst stage. Furthermore, it is showed that the histone H3 lysine 18 crotonylation (H3K18cr) modification is predominantly located in active promoter regions. It serves as an epigenetic hallmark of key transcriptional regulators and promotes the transcription activation of genes. Together, our results propose a model wherein P300-mediated histone crotonylation plays a crucial role in regulating the fate of embryonic development.
2024-06-18 | GSE241194 | GEO
Project description:Histone lysine crotonylation is a non-acetyl histone lysine modification that is evolutionarily conserved. It plays an important role in regulating various biological processes, including gene transcriptional regulation, spermatogenesis, and cell cycle. However, the dynamic changes and functions of histone crotonylation in preimplantation embryonic development in mammals remain unclear. In this study, we have shown that the transcription coactivator P300 functions as a writer of histone crotonylation during embryonic development. Depletion of P300 resulted in significant developmental defects and dysregulation of the transcriptome of embryos. Importantly, we demonstrated that P300 catalyzes the crotonylation of histone, directly stimulating transcription and regulating gene expression, thereby ensuring successful embryo development to the blastocyst stage. Furthermore, it is showed that the histone H3 lysine 18 crotonylation (H3K18cr) modification is predominantly located in active promoter regions. It serves as an epigenetic hallmark of key transcriptional regulators and promotes the transcription activation of genes. Together, our results propose a model wherein P300-mediated histone crotonylation plays a crucial role in regulating the fate of embryonic development.
2024-06-18 | GSE241193 | GEO
Project description:We examined the genome-wide distribution of histone crotonylation and H3K27ac in human embryonic stem cells and induced endoderm cells, by obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA. When compared to H3K27ac, histone crotonylation was more enriched in metabolic genes and in promoters at pluripotent state, while H3k27ac was enriched in the enhancers of endoderm genes. After endoderm differentiation, histone crotonylation and H3K27ac were both enriched in endoderm genes. Moreover, the enrichment of histone crotonylation was more remarkable than that of H3K27ac. Our data indicate that histone crotonylation correlates with endoderm differentiation.
2021-02-23 | GSE130344 | GEO