Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hexokinase 2 and lactate mediated gene expression via histone H3 lysine 18 lactylation (CHO CUT&Tag)

ABSTRACT: Hexokinase catalyzes the first committed step in glucose metabolism by phosphorylating glucose to produce glucose-6-phosphate. Highly glycolytic proliferating cells such as cancer cells take advantage of HK2 expression to accelerate glucose metabolism even in the presence of oxygen. This acceleration not only provides sufficient glycolytic intermediates to support the anabolic demands of the cells but also inevitably accompanies increased formation of metabolic end products such as lactate. Currently, the effect of lactate caused by HK2-mediated metabolic alteration is largely unknown. A recent study found that lactate plays a role in an epigenetic alteration known as histone lactylation. Here, using RNA-seq and CUT&Tag chromatin profiling, we study the effect of HK2 and lactate on gene expression via histone lactylation (H3K18la).

ORGANISM(S): Cricetulus griseus

PROVIDER: GSE229151 | GEO | 2023/05/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Hexokinase 2 and lactate mediated gene expression via histone H3 lysine 18 lactylation (CHO RNA-Seq)

Project description:Hexokinase catalyzes the first committed step in glucose metabolism by phosphorylating glucose to produce glucose-6-phosphate. Highly glycolytic proliferating cells such as cancer cells take advantage of HK2 expression to accelerate glucose metabolism even in the presence of oxygen. This acceleration not only provides sufficient glycolytic intermediates to support the anabolic demands of the cells but also inevitably accompanies increased formation of metabolic end products such as lactate. Currently, the effect of lactate caused by HK2-mediated metabolic alteration is largely unknown. A recent study found that lactate plays a role in an epigenetic alteration known as histone lactylation. Here, using RNA-seq and CUT&Tag chromatin profiling, we study the effect of HK2 and lactate on gene expression via histone lactylation (H3K18la).

2023-05-05 | GSE229153 | GEO

Hexokinase 2-mediated gene expression via histone lactylation is required for hepatic stellate cell activation and liver fibrosis (CUT&Tag)

Project description:Lactate was implicated in activation of hepatic stellate cells (HSCs). However, the mechanism by which lactate exerts its effect remains elusive. We show that hexokinase 2 (HK2) is sufficient to change gene expression by histone lactylation but not histone acetylation. Using RNA-seq and CUT&Tag chromatin profiling, we found that induction of HK2 expression in activated HSCs is required for the induced gene expression by elevating histone lactylation. Inhibiting histone lactylation by Hk2 deletion or pharmacological inhibition of lactate production diminishes HSC activation, whereas exogenous lactate but not acetate supplementation rescues the activation phenotype. Thus, lactate produced by activated HSCs determines the HSC fate via histone lactylation. We found that histone acetylation competes with histone lactylation, which could explain why class I HDAC inhibitors impede HSC activation. Finally, HSC-specific or systemic deletion of HK2 inhibits HSC activation and liver fibrosis in vivo. Therefore, we provide evidence that HK2 may be an effective therapeutic target for liver fibrosis.

2023-05-05 | GSE229154 | GEO

Hexokinase 2-mediated gene expression via histone lactylation is required for hepatic stellate cell activation and liver fibrosis (HSC-RNA-Seq)

2023-05-05 | GSE229155 | GEO

Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma

Project description:Macrophages are critical components of the immunosuppressive microenvironment that restrict anti-cancer immunity in glioblastoma (GBM). However, how GBM shapes the regulatory function of macrophages remains elusive. Here, we report that monocyte-derived macrophages (MDM), but not yolk-sac derived microglia (MG), exhibited potent immunosuppressive activity, which was mediated by a population of glycolytic GLUT1+MDM, in an IL10-dependent manner. GBM-derived factors reprogrammed MDM towards glycolytic cells with enhanced avidity for glucose, which was mostly used to generate lactate. In turn, intracellular lactate caused lactylation of histone lysine residues that promoted MDM immunosuppressive activity via regulation of Il10 expression. GBM-primed activation of PERK supported glucose metabolism and regulated GLUT1 expression through ATF4 in MDM. PERK-deletion in MDM abrogated histone lactylation and suppressive activity, thereby promoting polyfunctional T cell-infiltration of tumors. In combination with immunotherapy, PERK-deletion blocked GBM progression. Our study demonstrates that glucose-driven histone lactylation controls MDM immunosuppressive function; all in a PERK-dependent manner.

2024-05-06 | GSE260700 | GEO

Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in brain tumors [RNA-seq]

2024-05-06 | GSE260701 | GEO

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

Project description:After injury, muscles require fully functional macrophages to recover completely. During muscle regeneration, macrophages transition from a pro-inflammatory to a pro-restorative phenotype ensures the proper regeneration. Lactate is a crucial molecule for muscle-residing macrophage polarisation. Histone lactylation, a direct derivative of lactate, has been implicated in macrophage polarisation in vitro . In this work, we show for the first time that macrophages recruited to the muscle after ischemic injury modify their histone lactylome between 2 and 4 days post injury. Absolute histone lactylation levels increase significantly. Although subtly, also the genomic enrichment of H3K18la changes from 2 to 4 days post injury and this correlates with gene expression changes. Interestingly, we find that H3K18la genomic enrichment changes from day 2 to day 4 post injury are predictive for gene expression changes later in time, from day 4 to day 7, rather than being a reflection of past gene expression changes from day 1 to day 2. Our results suggest that histone lactylation dynamics are functionally important for the resolving action of macrophages during muscle regeneration.

2024-04-08 | GSE254129 | GEO

Macrophage histone lactylation during ischemia induced-muscle regeneration [RNA-Seq]

2024-04-08 | GSE254128 | GEO

Metabolic regulation of gene expression by histone lactylation

Project description:Cancer-augmented lactogenesis has been described by the Warburg effect, and is associated with several major hallmarks of neoplasia. However, the non-metabolic functions of elevated lactate in physiology and disease remain unknown. Here we report histone lysine lactylation as a new type of epigenetic mechanism and as a functional destination for lactate. Histone lactylation is induced under glycolytic conditions such as hypoxia and M1 macrophage polarization. In the late phase of M1 macrophage polarization, increases in histone lactylation but not acetylation mark M2-like genes for activation. Our findings suggest a feedback mechanism of the innate immune system to switch from proinflammation to resolution through histone Kla-associated gene expression. This mechanism is implemented by the coopted function of lactate and histone lactylation in metabolism and epigenetics. Together, our study opens a new avenue for understanding function of lactate and glycolysis underlined diverse pathophysiological conditions.

2019-08-06 | GSE115354 | GEO

Glycolysis-stimulated Esrrb Lactylation Promotes the Self-renewal and XEN Differentiation of Embryonic Stem Cells

Project description:Embryonic stem cells (ESCs) favor glycolysis over oxidative phosphorylation for energy production, and glycolytic metabolism is critical for pluripotency establishment, maintenance and exit. However, how glycolysis regulates the self-renewal and differentiation of ESCs remains elusive. Here, we demonstrated that protein lactylation, regulated by intracellular lactate, contributes to the self-renewal of ESCs. Next, the lactylome profiles of ESCs with and without a lactate dehydrogenase (Ldh) inhibitor, which suppresses the conversion of pyruvate to lactate, were depicted. It was notable that many lactylated proteins are involved in the self-renewal and differentiation of ESCs. We further showed that Esrrb, an orphan nuclear receptor involved in pluripotency maintenance and extraembryonic endoderm stem cell (XEN) differentiation, is lactylated on K228 and K232. Lactylation of Esrrb enhances its activity in promoting ESC self-renewal in the absence of LIF and XEN differentiation of ESCs, through increasing its binding at target genes. Our studies reveal the importance of protein lactation in the self-renewal and XEN differentiation of ESCs, and the underlying mechanism for glycolytic metabolism regulating cell fate choice.

2024-03-01 | GSE237618 | GEO

microRNA-143 downregulates Hexokinase 2 in colon cancer cells

Project description:MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in tumorigenesis. miR-143 is reported to be down-regulated in several cancers, but knowledge of its targets in colon cancer remains limited. To investigate the role of miR-143 in colon cancer, we have employed a microarray based approach to identify miR-143 targets. Based on seed site enrichment analyses and unbiased word analyses, we found a significant enrichment of miRNA binding sites in the 3M-bM-^@M-^Y-untranslated regions (UTRs) of transcripts down-regulated upon miRNA overexpression. Here we identify Hexokinase 2 (HK2) as a direct target of miR-143 and show that re-introduction of miR-143 in the colon cancer cell line DLD-1 results in a decreased lactate secretion, indicating that miR-143 down-regulation of HK2 affects glucose metabolism in colon cancer cells. DLD-1 cells were transfected with 50 nM miR-143 duplex or mock transfected. Total RNA was harvested 24 hours post-transfection and analyzed on Affymetrix HG-U133 Plus 2.0 human arrays.

2012-05-01 | E-GEOD-33420 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data