Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Impact of ATP-citrate lyase catalytic activity and serine 455 phosphorylation on histone acetylation and inflammatory responses in human monocytic cells

ABSTRACT: Impact of ATP-citrate lyase catalytic activity and serine 455 phosphorylation on histone acetylation and inflammatory responses in human monocytic cells

PROVIDER: PRJNA891688 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR21949300.fastq.gz	Fastqsanger.gz
	SRR21949301.fastq.gz	Fastqsanger.gz
	SRR21949302.fastq.gz	Fastqsanger.gz
	SRR21949303.fastq.gz	Fastqsanger.gz
	SRR21949304.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 32

Similar Datasets

Impact of ATP-citrate lyase catalytic activity and serine 455 phosphorylation on histone acetylation and inflammatory responses in human monocytic cells

Project description:ATP-citrate lyase (ACLY) is a key enzyme provoking metabolic and epigenetic gene regulation. Molecularly, these functions are exerted by the provision of acetyl-coenzyme A, which is then used as a substrate for de novo lipogenesis or as an acetyl-group donor in acetylation reactions. It has been demonstrated that ACLY activity can be positively regulated via phosphorylation at serine 455 by Akt and protein kinase A. Nonetheless, the impact of phosphorylation on ACLY function in human myeloid cells is poorly understood. In this study we reconstituted ACLY knockout human monocytic THP-1 cells with a wild type ACLY as well as catalytically inactive H760A, and phosphorylation-deficient S455A mutants. Using these cell lines, we determined the impact of ACLY activity and phosphorylation on histone acetylation and pro-inflammatory gene expression in response to lipopolysaccharide (LPS). Our results show that ACLY serine 455 phosphorylation does not influence the proper enzymatic function of ACLY, since both, wild type ACLY and phosphorylation-deficient mutant, exhibited increased cell growth and histone acetylation as compared to cells with a loss of ACLY activity. Transcriptome analysis revealed enhanced expression of pro-inflammatory and interferon response genes in ACLY knockout and H760A THP-1 cells under unstimulated or LPS-treated conditions. At the same time, S455A ACLY-expressing cells showed a phenotype very similar to wild type cells. Contrary to ACLY knockout, pharmacological inhibition of ACLY in THP-1 cells or in primary human macrophages does not enhance LPS-triggered pro-inflammatory gene expression. Our data thus suggest that ACLY retains functionality in the absence of Akt/PKA-mediated phosphorylation in human myeloid cells. Furthermore, loss of ACLY activity may elicit long-term adaptive mechanisms, increasing inflammatory responses.

2022-11-30 | GSE216003 | GEO

Toll-like receptor signaling rewires macrophage metabolism and promotes histone acetylation via ATP-citrate lyase

Project description:TLR activation induces inflammatory responses in macrophages by activating temporally defined transcriptional cascades within the first hours after stimulation. Whether concurrent changes in the cellular metabolism that occur upon TLR activation influence the quality of the transcriptional responses remain unknown. Here we investigated how macrophages adopt their metabolism early after activation to regulate TLR-inducible gene induction. Macrophages increase glucose metabolism and adopt fluxes through the TCA cycle to foster Citrate synthesis. We concomitantly observe activation of ATP-Citrate Lyase (Acly), resulting in augmented acetyl-CoA synthesis and histone acetylation. To investigate which genes and genes classes require ATP-citrate lyase activity for induction we stimulated bone marrow derived macrophages with LPS after ATP-citrate lyase inhibition.

2019-12-16 | GSE129497 | GEO

Macrophage ATP citrate lyase deficiency stabilizes atherosclerotic plaques

Project description:Macrophage ATP citrate lyase deficiency stabilizes atherosclerotic plaques

| PRJNA522993 | ENA

Selective autophagic degradation of ATP citrate lyase maintains citrate homeostasis and promotes oocyte maturation

Project description:Selective autophagic degradation of ATP citrate lyase maintains citrate homeostasis and promotes oocyte maturation

| PRJNA787974 | ENA

Selective autophagic degradation of ATP citrate lyase maintains citrate homeostasis and promotes oocyte maturation

Project description:Autophagy is a cellular and energy homeostatic mechanism that contributes to maintain the number of primordial follicles, germ cell survival, and anti-ovarian aging. However, it remains unknown whether autophagy in granulosa cells affects the oocyte maturation. Here, we show a clear tendency of reduced autophagy level in human granulosa cell from women of advanced maternal age, implying a potential negative correlation between autophagy level and oocyte quality. We therefore established a co-culture system and show that either pharmacological inhibition or genetic ablation of autophagy in granulosa cells negatively affect the oocyte quality and fertilization ability. Moreover, our metabolomics analysis indicates that the adverse impact of autophagy impairment on oocyte quality is mediated by downregulated citrate levels, while exogenous supplementation of citrate can significantly restore the oocyte maturation. In molecular level, we found ATP citrate lyase (Acly), which is a crucial enzyme catalyzing the cleavage of citrate, was preferentially associated with K63-linked ubiquitin chains and recognized by the autophagy receptor protein SQSTM1/p62 for the selective autophagic degradation. In human follicles, autophagy levels in granulosa cells was downregulated with maternal aging, accompanied by decreased citrate in the follicular fluid, implying a potential correlation between citrate metabolism and oocyte quality. We also show that elevated citrate levels in porcine follicular fluid promote oocyte maturation. Collectively, our data reveal that autophagy in granulosa cells is a beneficial mechanism to maintain a certain degree of citrate by selectively targeting Acly during oocyte maturation.

2023-01-09 | GSE190697 | GEO

Macrophage ATP citrate lyase deficiency stabilizes atherosclerotic plaques

Project description:Macrophages represent a major immune cell population in atherosclerotic plaques and play central role in the progression of this lipid-driven chronic inflammatory disease. Targeting immunometabolism is proposed as a strategy to revert aberrant macrophage activation to improve disease outcome. Here, we show ATP citrate lyase (Acly) to be activated in inflammatory macrophages and human atherosclerotic plaques. We demonstrate that myeloid Acly deficiency induces a stable plaque phenotype characterized by increased collagen deposition and fibrous cap thickness, along with a smaller necrotic core. In-depth functional, lipidomic, and transcriptional characterization indicate deregulated fatty acid and cholesterol biosynthesis and reduced liver X receptor (LXR) activation within the macrophages in vitro. This results in macrophages that are more prone to undergo apoptosis, whilst presenting increased phagocytosis of apoptotic cells. Together, our results indicate that targeting macrophage metabolism improves atherosclerosis outcome and we reveal Acly as a promising therapeutic target to stabilize atherosclerotic plaques.

2020-02-18 | GSE126690 | GEO

ATP Citrate Lyase Drives Vascular Remodeling Diseases Development Through Metabolic-Epigenetic Reprograming.

Project description:ATP Citrate Lyase Drives Vascular Remodeling Diseases Development Through Metabolic-Epigenetic Reprograming.

| PRJNA1072687 | ENA

RNA-seq analysis of Schwann cell knockout of ATP citrate lyase (ACLY)

Project description:RNA-seq analysis of Schwann cell knockout of ATP citrate lyase (ACLY)

| PRJNA1058573 | ENA

The role of ATP citrate lyase in myelin formation and maintenance

Project description:Schwann cell-specific knockout of ATP citrate lyase (ACLY) revealed that this pathway is important for myelin maintenance rather than formation, and ACLY is required to maintain expression of a myelin-associated gene program.

2024-05-03 | MSV000094670 | MassIVE

ATP-Citrate lyase fuels axonal transport across species

Project description:Microtubule (MT)-based transport is an evolutionary conserved processed finely tuned by posttranslational modifications. Among them, tubulin acetylation, which is catalyzed by the α-tubulin N-acetyltransferase 1, Atat1, facilitates the recruitment and processivity of molecular motors along MT tracks. However, the mechanisms that controls Atat1 activity remains poorly understood. Here we show that a pool of vesicular ATP-citrate lyase Acly acts as a rate limiting enzyme to modulate Atat1 activity by controlling availability of Acetyl-CoA. In addition, we showed that Acly expression is reduced upon loss of Elongator activity, further connecting Elongator to Atat1 in the pathway regulating -tubulin acetylation and MT-dependent transport in projection neurons across species. Remarkably, comparable defects occur in fibroblasts from Familial Dysautonomia (FD) patients bearing an autosomal recessive mutation in the gene coding for the Elongator subunit ELP1. Our data may thus shine new light on the pathophysiological mechanisms underlying FD.

2022-02-16 | PXD021186 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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