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

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

PROVIDER: PRJNA1078281 | ENA |

REPOSITORIES: ENA

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

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

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

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

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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 |

Epigenetic regulators of clonal hematopoiesis control CD8 T cell stemness during immunotherapy [CUT&Tag]

Project description:Epigenetic regulators of clonal hematopoiesis control CD8 T cell stemness during immunotherapy [CUT&Tag]

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HCT116_SMARCA4 CUT&Tag

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scNanoSeq-CUT&Tag: a long-read single-cell CUT&Tag sequencing method for efficient chromatin modification profiling within individual cells

Project description:We developed scNanoSeq-CUT&Tag, a streamlined method by adapting a modified CUT&Tag protocol to Oxford Nanopore sequencing platform for efficient chromatin modification profiling at single-cell resolution. We firstly tested the performance of scNanoSeq-CUT&Tag on six human cell lines: K562, 293T, GM12878, HG002, H9, HFF1 and adult mouse blood cells, it showed that scNanoSeq-CUT&Tag can accurately distinguish different cell types in vitro and in vivo. Moreover, scNanoSeq-CUT&Tag enables to effectively map the allele-specific epigenomic modifications in the human genome andallows to analyze co-occupancy of histone modifications. Taking advantage of long-read sequencing,scNanoSeq-CUT&Tag can sensitively detect epigenomic state of repetitive elements. In addition, by applying scNanoSeq-CUT&Tag to testicular cells of adult mouse B6D2F1, we demonstrated that scNanoSeq-CUT&Tag maps dynamic epigenetic state changes during mouse spermatogenesis. Finally, we exploited the epigenetic changes of human leukemia cell line K562 during DNA demethylation, it showed that NanoSeq-CUT&Tag can capture H3K27ac signals changes along DNA demethylation. Overall, we prove that scNanoSeq-CUT&Tag is a valuable tool for efficiently probing chromatin state changes within individual cells.

2024-09-06 | GSE249799 | GEO

HIF2A(EPAS1) Genome-Wide Localization in MRC5 Human Fibroblasts by Cut & Tag

Project description:HIF2A(EPAS1) geenome_wide localization by Cut & Tag in MRC5 human fibroblasts ectopically expressing HIF2A in the pBabe vector, and in control MRC5 human fibroblasts containing only the pBabe vector. 2 biological replicates were done for the MRC5-HIF2A cells. Cut & Tag with an anti-H3-K27me3 Ab was done as a positive control for the Cut & Tag experiments.

2025-01-17 | E-MTAB-13732 | biostudies-arrayexpress

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