Lactate Modulates Transcriptional Regulation through H3K14ac
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE308678 | GEO | 2026/08/22
REPOSITORIES: GEO
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Project description:Lactate Modulates Transcriptional Regulation through H3K14ac
| PRJNA1332444 | ENA
Project description:Histone acetylation, including acetylated H3K14 (H3K14ac), is generally linked to gene activation. Monomethylated histone H3 lysine 4 (H3K4me1), together with other gene-activating marks, denotes active genes. In contrast to usual gene-activating functions of H3K14ac and H3K4me1, we here show that the dual histone modification mark H3K4me1-H3K14ac is recognized by ZMYND8 (also called RACK7) and functions to counteract gene expression. We identified ZMYND8 as a transcriptional corepressor of the H3K4 demethylase JARID1D. ZMYND8 antagonizes the expression of metastasis-linked genes, and its knockdown increases the cellular invasiveness in vitro and in vivo. The plant homeodomain (PHD) and Bromodomain cassette in ZMYND8 mediates the combinatorial recognition of H3K4me1-H3K14ac and H3K4me0-H3K14ac by ZMYND8. These findings uncover an unexpected role for the signature H3K4me1-H3K14ac in attenuating gene expression and reveal a previously unknown metastasis-suppressive epigenetic mechanism in which ZMYND8's PHD-Bromo cassette couples H3K4me1-H3K14ac with repression of metastasis-linked genes. i) ChIP-Seq data of ZMYND8, JARID1D, H3K4me1, H3K14ac, H3K4me3, and H3K27me3 in normal DU145 cells. ii) ChIP-Seq data of H3K4me1 and H3K4me3 in shLuciferase-, shJARID1D-, or shZMYND8-treated DU145 cells. iii) RNA-Seq data in shLuciferase-, shJARID1D-, or shZMYND8-treated DU145 cells.
2016-07-28 | E-GEOD-82260 | biostudies-arrayexpress
Project description:Histone acetylation, including acetylated H3K14 (H3K14ac), is generally linked to gene activation. Monomethylated histone H3 lysine 4 (H3K4me1), together with other gene-activating marks, denotes active genes. In contrast to usual gene-activating functions of H3K14ac and H3K4me1, we here show that the dual histone modification mark H3K4me1-H3K14ac is recognized by ZMYND8 (also called RACK7) and functions to counteract gene expression. We identified ZMYND8 as a transcriptional corepressor of the H3K4 demethylase JARID1D. ZMYND8 antagonizes the expression of metastasis-linked genes, and its knockdown increases the cellular invasiveness in vitro and in vivo. The plant homeodomain (PHD) and Bromodomain cassette in ZMYND8 mediates the combinatorial recognition of H3K4me1-H3K14ac and H3K4me0-H3K14ac by ZMYND8. These findings uncover an unexpected role for the signature H3K4me1-H3K14ac in attenuating gene expression and reveal a previously unknown metastasis-suppressive epigenetic mechanism in which ZMYND8's PHD-Bromo cassette couples H3K4me1-H3K14ac with repression of metastasis-linked genes.
2016-07-28 | GSE82260 | GEO
Project description:SPT6 (suppressor of Ty 6) is a conserved histone chaperone that facilitates transcription elongation, nucleosome reassembly, and RNA polymerase II progression. The functions of SPT6 in regulating chromatin remain not fully understood. Here we show that SPT6 localized to H3K14Ac enriched regions and promoted H3K14Ac densities in mouse embryonic stem cells (mESCs). Loss of SPT6 results in decreased H3K14Ac and transcription. Mechanistically, we showed that SPT6 enhances the chromatin binding levels of acetyltransferases KAT7 and KAT6A/KAT6B. In addition, we showed that SPT6 also promotes H3K14Ac in a KAT7/6A/6B independent manner. Our findings identify a vital role of SPT6 in maintaining the integrity of H3K14Ac profile in mESCs, thus suggesting a crosstalk between transcription machinery and H3K14Ac in mammals.
2025-05-22 | GSE282181 | GEO
Project description:SPT6 (suppressor of Ty 6) is a conserved histone chaperone that facilitates transcription elongation, nucleosome reassembly, and RNA polymerase II progression. The functions of SPT6 in regulating chromatin remain not fully understood. Here we show that SPT6 localized to H3K14Ac enriched regions and promoted H3K14Ac densities in mouse embryonic stem cells (mESCs). Loss of SPT6 results in decreased H3K14Ac and transcription. Mechanistically, we showed that SPT6 enhances the chromatin binding levels of acetyltransferases KAT7 and KAT6A/KAT6B. In addition, we showed that SPT6 also promotes H3K14Ac in a KAT7/6A/6B independent manner. Our findings identify a vital role of SPT6 in maintaining the integrity of H3K14Ac profile in mESCs, thus suggesting a crosstalk between transcription machinery and H3K14Ac in mammals.
2025-05-22 | GSE282180 | GEO
Project description:SPT6 (suppressor of Ty 6) is a conserved histone chaperone that facilitates transcription elongation, nucleosome reassembly, and RNA polymerase II progression. The functions of SPT6 in regulating chromatin remain not fully understood. Here we show that SPT6 localized to H3K14Ac enriched regions and promoted H3K14Ac densities in mouse embryonic stem cells (mESCs). Loss of SPT6 results in decreased H3K14Ac and transcription. Mechanistically, we showed that SPT6 enhances the chromatin binding levels of acetyltransferases KAT7 and KAT6A/KAT6B. In addition, we showed that SPT6 also promotes H3K14Ac in a KAT7/6A/6B independent manner. Our findings identify a vital role of SPT6 in maintaining the integrity of H3K14Ac profile in mESCs, thus suggesting a crosstalk between transcription machinery and H3K14Ac in mammals.
2025-05-22 | GSE282178 | GEO
Project description:SPT6 (suppressor of Ty 6) is a conserved histone chaperone that facilitates transcription elongation, nucleosome reassembly, and RNA polymerase II progression. The functions of SPT6 in regulating chromatin remain not fully understood. Here we show that SPT6 localized to H3K14Ac enriched regions and promoted H3K14Ac densities in mouse embryonic stem cells (mESCs). Loss of SPT6 results in decreased H3K14Ac and transcription. Mechanistically, we showed that SPT6 enhances the chromatin binding levels of acetyltransferases KAT7 and KAT6A/KAT6B. In addition, we showed that SPT6 also promotes H3K14Ac in a KAT7/6A/6B independent manner. Our findings identify a vital role of SPT6 in maintaining the integrity of H3K14Ac profile in mESCs, thus suggesting a crosstalk between transcription machinery and H3K14Ac in mammals.
2025-05-22 | GSE282179 | GEO
Project description:Lactate is abundant in the tumor environment as the secreted product of fermentative cells. In prostate cancer (PCa), cancer-associated fibroblasts are the major contributors and this secreted lactate is uptaken by cancer cells to sustain their mitochondrial metabolism. However, how lactate controls the metabolic and transcriptional regulation in tumors is far to be elucidated. Here, we identify an innovative lactate-driven mechanism able to increase the expression of genes involved in lipid metabolism in PCa cells. This regulation enhances intracellular lipid accumulation in lipid droplets (LDs) and provides acetyl moieties for histone acetylation, establishing a regulatory loop between metabolites and epigenetic control. Interestingly, inhibition of this loop by targeting bromodomains histone acetylation readers suppresses the expression of perilipin-2 (PLIN2), a crucial component of LDs, disrupting the lactate-dependent lipid metabolic rewiring. Since this metabolic-epigenetic regulatory loop sustains PCa metastatic potential, its targeting is of clinical relevance as demonstrated by the inhibition of PCa invasive potential in vivo. Overall, our findings show that lactate has both a metabolic and an epigenetic role in promoting PCa progression.
2022-01-31 | GSE195639 | GEO
Project description:Histone deacetylases (HDACs) play a major role in a wide range of cellular and developmental processes, often as master regulators of gene transcription. These epigenetic modifiers, which include eleven canonical HDACs and seven sirtuins (SIRTs), are commonly studied in cancer, especially by using nonselective HDAC inhibitor drugs. However, HDACs and SIRTs are also thought to be influential in cardiac function and pathology, yet the specific roles of individual HDACs have not been robustly probed in cardiomyocytes. In this study, we report the transcriptomic effects of individual HDAC/SIRT knockdowns in human induced pluripotent stem cell derived cardiomyocytes.
2026-03-12 | GSE309350 | GEO
Project description:Lactic acidosis, driven by hyperlactatemia, is a hallmark of severe Plasmodium falciparum malaria, yet its impact on parasitic life cycle and gene expression remains unclear. In mammalian cells, lactate influences transcription through histone lactylation, a novel post-translational modification. In this study, we demonstrate that P. falciparum undergoes lactate-derived lysine lactylation on nuclear proteins, including histones, histone variants, and AP2 transcription factors, with lactylation levels dynamically varying in response to physiological lactate ranges. Through CUT&RUN profiling, we show that elevated lactate enhances chromatin occupancy of lactylated proteins at promoters of genes involved in virulence and cytoadherence. Correspondingly, transcriptomic analyses demonstrated a suppression of these genes in response to elevated lactate, a pattern also evident in clinical isolates from severe malaria patients. Functionally, we demonstrate that high lactate reduces the binding ability of infected erythrocytes to CD36 receptor. Together, our findings reveal protein lactylation as a metabolite-responsive epigenetic mechanism in P. falciparum, linking host metabolic state to transcriptional reprogramming with direct implications for parasite virulence and disease pathogenesis.
2025-08-08 | GSE304394 | GEO