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Genome-wide maps of histone lactylation in ocular melanoma by CUT&Tag

ABSTRACT: Genome-wide maps of histone lactylation in ocular melanoma by CUT&Tag

PROVIDER: PRJNA1011208 | ENA |

REPOSITORIES: ENA

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Genome-wide maps of histone lactylation in ocular melanoma by CUT&Tag

Project description:To investigate the function of histone lactylation in ocular melanoma, we analyzed histone lactylation enrichment level in ocular melanoma by CUT&Tag.

2023-09-04 | GSE242018 | GEO

Genome-wide maps of histone lactylation in ocular melanoma by CHIP-seq

Project description:To investigate the function of histone lactylation in ocular melanoma, we analyzed histone lactylation enrichment level in ocular melanoma by CHIP-seq.

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Genome-wide maps of histone lactylation in ocular melanoma

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Genome-wide maps of histone lactylation in ocular melanoma

Project description:Genome-wide maps of histone lactylation in ocular melanoma

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DPF2 reads histone lactylation to drive transcription and tumorigenesis [CUT&TAG]

Project description:Lysine lactylation (Kla) is a new type of histone mark implicated in the regulation of various functional processes such as transcription. However, how this histone mark acts in cancers remains unexplored due in part to a lack of knowledge about its reader proteins. Here, we observe that cervical cancer (CC) cells undergo metabolic reprogram by which lactate accumulation and thereby boost histone lactylation, particularly H3K14la. Utilizing a multivalent photoaffinity probe in combination with quantitative proteomics approach, we identify DPF2 as a candidate target of H3K14la. Biochemical studies as well as CUT&Tag analysis reveal that DPF2 is capable of binding to H3K14la, and co-localizes with it on promoters of oncogenic genes. Notably, disrupting the association between DPF2 and histone lactylation through structure-guided mutation blunts those cancer-related gene expression along with cell survival. Together, our findings reveal DPF2 as a bona fide H3K14la effector that couples histone lactylation to gene transcription and cell survival, offering insight into how histone Kla engages in transcription and tumorigenesis.

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Histone lactylation mediated by Fam172a in POMC neurons regulates energy balance [CUT&TAG]

Project description:Glycolysis-derived lactate was identified as substrate for histone lactylation, which has been regarded as a significant role in transcriptional regulation in many tissues. However, the role of histone lactylation in the metabolic center, the hypothalamus, is still unknown. Here, we show that hypothalamic pro-opiomelanocortin (POMC) neuron-specific deletion of family with sequence similarity 172, member A (Fam172a) can increase histone lactylation and protect mice against diet-induced obesity (DIO) and related metabolic disorders. Conversely, overexpression of Fam172a in POMC neurons led to an obesity-like phenotype. Using RNA-seq and CUT&Tag chromatin profiling analyses, we find that knockdown of Fam172a activates the glycolytic process and increases peptidylglycine α-amidating monooxygenase (PAM), which affects the synthesis of α-MSH, via H4K12la (histone lactylation). In addition, pharmacological inhibition of lactate production clearly abrogates the anti-obesity effect of PFKO (POMC-Cre, Fam172aloxP/loxP, POMC neurons Fam172a knockout). These findings highlight the importance of Fam172a and lactate in the development of obesity.

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histone lactylation in ocular melanoma

Project description:histone lactylation in ocular melanoma

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Project description:Cancer cells often rely on aerobic glycolysis for metabolism, and lactylation, a newly discovered post-translational modification, significantly impacts molecular processes. This study comprehensively analyzes lactylation's role in oral squamous cell carcinoma (OSCC), providing initial insights into its impact on progression. Oral squamous cell carcinoma cell lines, before and after lactate treatment, underwent CUT&TAG, ATAC, and transcriptomic sequencing. ChIP-qPCR and RT-qPCR validated results in OSCC tissues. Integrated analysis identified 217 genes with increased expression driven by lactylation in OSCC. Lactylation broadly impacted pathways in cancer, notably regulating PI3K/AKT and MAPK signaling. This pioneering study analyzes lactylation in OSCC, providing a global map of its regulation in oral squamous cell carcinoma from the perspective of chromatin-driven gene expression.

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Project description:Macrophage histone lactylation during ischemia induced-muscle regeneration [CUT&Tag]

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