Glucose starvation induces a switch in the histone acetylome for activation of gluconeogenic and fat metabolism genes.

Acetyl-CoA is a key intermediate situated at the intersection of many metabolic pathways. The reliance of histone acetylation on acetyl-CoA enables the coordination of gene expression with metabolic state. Abundant acetyl-CoA has been linked to the activation of genes involved in cell growth or tumorigenesis through histone acetylation. However, the role of histone acetylation in transcription under low levels of acetyl-CoA remains poorly understood. Here, we use a yeast starvation model to observe the dramatic alteration in the global occupancy of histone acetylation following carbon starvation; the location of histone acetylation marks shifts from growth-promoting genes to gluconeogenic and fat metabolism genes. This reallocation is mediated by both the histone deacetylase Rpd3p and the acetyltransferase Gcn5p, a component of the SAGA transcriptional coactivator. Our findings reveal an unexpected switch in the specificity of histone acetylation to promote pathways that generate acetyl-CoA for oxidation when acetyl-CoA is limiting.

• Publication year

  2022

• Venue

  Molecules and Cells

• Publication date

  2022-01-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.molcel.2021.12.015PMID 34995509PMCID PMC8794035
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• A Class I Histone Deacetylase Inhibitor Attenuates Insulin Resistance and Inflammation in Palmitate-Treated C2C12 Myotubes and Muscle of HF/HFr Diet Mice

  2020cited by this paper
• Sink into the Epigenome: Histones as Repositories That Influence Cellular Metabolism.

  2018cited by this paper
• ACSS2 promotes systemic fat storage and utilization through selective regulation of genes involved in lipid metabolism

  2018cited by this paper
• Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi

  2018cited by this paper
• The impact of cellular metabolism on chromatin dynamics and epigenetics

  2017cited by this paper
• SAGA is a general cofactor for RNA polymerase II transcription

  2017cited by this paper
• Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy.

  2017cited by this paper
• ACETYL-COA SYNTHETASE REGULATES HISTONE ACETYLATION AND HIPPOCAMPAL MEMORY

  2017cited by this paper
• Histone Deacetylase Inhibitors as Anticancer Drugs

  2017cited by this paper
• Histone Deacetylase 1 (HDAC1) Negatively Regulates Thermogenic Program in Brown Adipocytes via Coordinated Regulation of Histone H3 Lysine 27 (H3K27) Deacetylation and Methylation*

  2016cited by this paper
• HDACs and HDAC Inhibitors in Cancer Development and Therapy.

  2016cited by this paper
• Metabolic control of methylation and acetylation.

  2016cited by this paper
• deepTools2: a next generation web server for deep-sequencing data analysis

  2016cited by this paper
• Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown

  2016cited by this paper
• Acetyl-CoA and the Regulation of Metabolism: Mechanisms and Consequences

  2015cited by this paper
• The MEME Suite

  2015cited by this paper
• An Interactive Database for the Assessment of Histone Antibody Specificity.

  2015cited by this paper
• Glucose repression in Saccharomyces cerevisiae

  2015cited by this paper
• Global Promoter Targeting of a Conserved Lysine Deacetylase for Transcriptional Shutoff during Quiescence Entry.

  2015cited by this paper
• Sambamba: fast processing of NGS alignment formats

  2015cited by this paper
• Regulation of autophagy by cytosolic acetyl-coenzyme A.

  2014cited by this paper
• Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

  2014cited by this paper
• New and emerging HDAC inhibitors for cancer treatment.

  2014cited by this paper
• High temporal-resolution view of transcription and chromatin states across distinct metabolic states in budding yeast

  2014cited by this paper
• The SAGA coactivator complex acts on the whole transcribed genome and is required for RNA polymerase II transcription

  2014cited by this paper
• Gcn5 and sirtuins regulate acetylation of the ribosomal protein transcription factor Ifh1.

  2013cited by this paper
• featureCounts: an efficient general purpose program for assigning sequence reads to genomic features

  2013cited by this paper
• Integration of multiple nutrient cues and regulation of lifespan by ribosomal transcription factor Ifh1.

  2013cited by this paper
• Inferring direct DNA binding from ChIP-seq

  2012cited by this paper
• Identifying ChIP-seq enrichment using MACS

  2012cited by this paper
• Gatekeepers of chromatin: Small metabolites elicit big changes in gene expression.

  2012cited by this paper
• ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia

  2012cited by this paper
• clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters

  2012cited by this paper
• A comprehensive genomic binding map of gene and chromatin regulatory proteins in Saccharomyces.

  2011cited by this paper
• Analysing recombination in nucleotide sequences

  2011cited by this paper
• Transcriptional Regulation in Saccharomyces cerevisiae: Transcription Factor Regulation and Function, Mechanisms of Initiation, and Roles of Activators and Coactivators

  2011cited by this paper
• Histone modifications in cancer biology and prognosis.

  2011cited by this paper
• Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes.

  2011cited by this paper
• The Gcn5 Bromodomain of the SAGA Complex Facilitates Cooperative and Cross-tail Acetylation of Nucleosomes*

  2009cited by this paper
• ATP-Citrate Lyase Links Cellular Metabolism to Histone Acetylation

  2009cited by this paper
• The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men

  2008cited by this paper
• Coordination of growth rate, cell cycle, stress response, and metabolic activity in yeast.

  2008cited by this paper
• Histone modifications as markers of cancer prognosis: a cellular view

  2007cited by this paper
• Cyclic changes in metabolic state during the life of a yeast cell

  2007cited by this paper
• The role of histone deacetylases (HDACs) in human cancer

  2007cited by this paper
• Nucleocytosolic acetyl-coenzyme a synthetase is required for histone acetylation and global transcription.

  2006cited by this paper
• SwissRegulon: a database of genome-wide annotations of regulatory sites

  2006cited by this paper
• Global histone modification patterns predict risk of prostate cancer recurrence

  2005cited by this paper
• The YEASTRACT database: a tool for the analysis of transcription regulatory associations in Saccharomyces cerevisiae

  2005cited by this paper
• A genome-wide housekeeping role for TFIID and a highly regulated stress-related role for SAGA in Saccharomyces cerevisiae.

  2004cited by this paper
• Theoretical and practical advances in genome halving

  2004cited by this paper
• Multiple Pathways Are Co-regulated by the Protein Kinase Snf1 and the Transcription Factors Adr1 and Cat8*

  2003cited by this paper
• Dynamics of histone acetylation in vivo. A function for acetylation turnover?

  2002cited by this paper
• Remodeling of yeast genome expression in response to environmental changes.

  2001cited by this paper
• Histone acetyltransferases.

  2001cited by this paper
• BIOINFORMATICS APPLICATIONS NOTE

  2001cited by this paper
• Translating the Histone Code

  2001cited by this paper
• Genomic expression programs in the response of yeast cells to environmental changes.

  2000cited by this paper
• An interlaboratory comparison of physiological and genetic properties of four Saccharomyces cerevisiae strains.

  2000cited by this paper
• The language of covalent histone modifications

  2000cited by this paper
• Acetylation of Histones and Transcription-Related Factors

  2000cited by this paper
• Histone acetylation and transcriptional regulatory mechanisms.

  1998cited by this paper
• Global Regulatory Functions of Oaf1p and Pip2p (Oaf2p), Transcription Factors That Regulate Genes Encoding Peroxisomal Proteins in Saccharomyces cerevisiae

  1998cited by this paper
• Additional modules for versatile and economical PCR‐based gene deletion and modification in Saccharomyces cerevisiae

  1998cited by this paper
• Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: characterization of an Ada complex and the SAGA (Spt/Ada) complex.

  1997cited by this paper
• Histone acetylation in chromatin structure and transcription

  1997cited by this paper
• Purification, Identification, and Properties of a Saccharomyces cerevisiae Oleate-activated Upstream Activating Sequence-binding Protein That Is Involved in the Activation of POX1(*)

  1996cited by this paper
• Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines

  1996cited by this paper
• The Saccharomyces cerevisiae ADR1 gene is a positive regulator of transcription of genes encoding peroxisomal proteins

  1991cited by this paper
• Histone function in transcription.

  1990cited by this paper

• Calorie Restriction Extends Lifespan in Yeast Independently of GCN5

  2026cites this paper
• Adaptive regulation of glycerophospholipid metabolism.

  2026cites this paper
• Synergistic regulation of carbohydrate metabolism by histone acetyltransferases FgSas3 and FgRtt109 in a mycotoxin-producing fungal pathogen

  2025cites this paper
• Metabolic mediators at the Nexus: How SAM, Acetyl-CoA, and NAD+ bridge phytohormone signaling and epigenetic regulation.

  2025cites this paper
• The histone modification regulator, SIN3, plays a role in the cellular response to changes in glycolytic flux

  2025cites this paper
• DDX1 Crotonylation Mediates ACOX1 Alternative Splicing through HNRNPK to Increase Peroxisomal Oxidative Damage.

  2025cites this paper
• The associations of diet quality and cardiometabolic indicators in children and the mediation role of cardiorespiratory fitness

  2025cites this paper
• TCA-cycle metabolites in the nucleus: drivers of chromatin and epigenetic control

  2025cites this paper
• The Role and Research Progress of Glycolytic Metabolic Reprogramming in Smooth Muscle Cells in Atherosclerosis

  2025cites this paper
• Beyond energy: how TCA cycle-derived metabolites regulate gene expression and inflammation in the nucleus

  2025cites this paper
• The role of lysine acetylation in metabolic sensing and proteostasis.

  2025cites this paper
• African walnut (Plukenetia conophora) oil improves glucose uptake and metabolic activities in erythrocytes

  2025cites this paper
• GCN5 Is a Master Regulator of Gene Expression in the Malaria Parasite Plasmodium falciparum

  2025cites this paper
• Temporal oscillation of phospholipids promotes metabolic efficiency

  2025cites this paper
• A two-step regulatory mechanism dynamically controls histone H3 acetylation by SAGA complex at growth-related promoters

  2025cites this paper
• Phospholipid Biosynthesis: An Unforeseen Modulator of Nuclear Metabolism

  2025cites this paper
• Moonlighting Enzymes at the Interface Between Metabolism and Epigenetics.

  2025cites this paper
• The histone modification regulator, SIN3, plays a role in the cellular response to changes in glycolytic flux

  2025cites this paper
• Massive changes in gene expression and their cause(s) can be a unifying principle in the pathobiology of Alzheimer's disease

  2025cites this paper
• O-GlcNAc and phosphorylation modifications on HtL1/FBA10 regulate wheat vernalization for flowering

  2025cites this paper
• Nucleoside Diphosphate Kinases Are ATP-Regulated Carriers of Short-Chain Acyl-CoAs

  2024cites this paper
• Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

  2024cites this paper
• ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma

  2024cites this paper
• Specific regulation of epigenome landscape by metabolic enzymes and metabolites

  2024cites this paper
• Grapevine cell response to carbon deficiency requires transcriptome and methylome reprogramming

  2024cites this paper
• Lysine acetylation of histone acetyltransferase adaptor protein ADA2 is a mechanism of metabolic control of chromatin modification in plants

  2024cites this paper
• Acetyl-CoA synthetase (ACSS2) does not generate butyryl- and crotonyl-CoA

  2024cites this paper
• Hyperacetylated histone H4 is a source of carbon contributing to lipid synthesis

  2024cites this paper
• MYST regulates DNA repair and forms a NuA4-like complex in the malaria parasite Plasmodium falciparum

  2024cites this paper
• PPARs as Key Transcription Regulators at the Crossroads of Metabolism and Inflammation

  2024cites this paper
• The SWI/SNF chromatin remodeling complex: a critical regulator of metabolism

  2024cites this paper
• Bacteria-derived short-chain fatty acids as potential regulators of fungal commensalism and pathogenesis.

  2024cites this paper
• Nuclear pyruvate dehydrogenase complex regulates histone acetylation and transcriptional regulation in the ethylene response

  2024cites this paper
• DNMT3A loss drives a HIF-1-dependent synthetic lethality to HDAC6 inhibition in non-small cell lung cancer

  2024cites this paper
• Targeting SNRNP200-induced splicing dysregulation offers an immunotherapy opportunity for glycolytic triple-negative breast cancer

  2024cites this paper
• The Zeb1-Cxcl1 axis impairs the antitumor immune response by inducing M2 macrophage polarization in breast cancer.

  2024cites this paper
• A two-way relationship between histone acetylation and metabolism.

  2024cites this paper
• Fantastic proteins and where to find them – histones, in the nucleus and beyond

  2024cites this paper
• Oncogenic IDH1mut drives robust loss of histone acetylation and increases chromatin heterogeneity

  2024cites this paper
• Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet

  2023cites this paper
• Plasmodium falciparum GCN5 plays a key role in regulating artemisinin resistance–related stress responses

  2023cites this paper
• The Illustration of Altered Glucose Dependency in Drug-Resistant Cancer Cells

  2023cites this paper
• The fruit fly acetyltransferase chameau promotes starvation resilience at the expense of longevity

  2023cites this paper
• Coordination of cross-talk between metabolism and epigenetic regulation by the SIN3 complex.

  2023cites this paper
• Plasmodium falciparum GCN5 plays a key role in regulating artemisinin resistance-related stress responses

  2023cites this paper
• The Saccharomyces cerevisiae acetyltransferase Gcn5 exerts antagonistic pleiotropic effects on chronological ageing

  2023influential citation
• Nuclear Pyruvate Dehydrogenase Complex Regulates Histone Acetylation and Transcriptional Regulation in the Ethylene Response

  2023cites this paper
• Increased histone acetylation is the signature of repressed state on the genes transcribed by RNA polymerase III.

  2023cites this paper
• Plasmodium falciparum gametocytes display global chromatin remodelling during sexual differentiation

  2023cites this paper
• Chromatin balances cell redox and energy homeostasis

  2023cites this paper
• Yeast zinc cluster transcription factors involved in the switch from fermentation to respiration show interdependency for DNA binding revealing a novel type of DNA recognition

  2023cites this paper
• Cytosolic acetyl-CoA synthetase (ACSS2) does not generate butyryl- and crotonyl-CoA

  2023cites this paper
• An enhanced network of energy metabolism, lysine acetylation, and growth-promoting protein accumulation is associated with heterosis in elite hybrid rice

  2023cites this paper
• Functional tug of war between kinases, phosphatases, and the Gcn5 acetyltransferase in chromatin and cell cycle checkpoint controls

  2023cites this paper
• S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress

  2023cites this paper
• Nrf2 drives hepatocellular carcinoma progression through acetyl-CoA-mediated metabolic and epigenetic regulatory networks.

  2023cites this paper
• Docosahexaenoic Acid Alters Lipid Metabolism Processes via H3K9ac Epigenetic Modification in Dairy Goat.

  2023cites this paper
• Roles of protein post-translational modifications in glucose and lipid metabolism: mechanisms and perspectives

  2023cites this paper
• The omics era: a nexus of untapped potential for Mendelian chromatinopathies

  2023cites this paper
• Shifting acetylation during starvation

  2022cites this paper
• Tup1 is critical for transcriptional repression in Quiescence in S. cerevisiae

  2022cites this paper
• Acetylation-Specific Interference by Anti-Histone H3K9ac Intrabody Results in Precise Modulation of Gene Expression

  2022cites this paper
• Insights Into the Biogenesis and Emerging Functions of Lipid Droplets From Unbiased Molecular Profiling Approaches

  2022cites this paper
• Mechanisms of gene regulation by histone degradation in adaptation of yeast: an overview of recent advances

  2022cites this paper
• Transcriptomic balance and optimal growth are determined by cell size

  2022cites this paper
• The ER-Mitochondria Interface as a Dynamic Hub for T Cell Efficacy in Solid Tumors

  2022cites this paper
• Glucose Starvation or Pyruvate Dehydrogenase Activation Induce a Broad, ERK5-Mediated, Metabolic Remodeling Leading to Fatty Acid Oxidation

  2022cites this paper
• Reciprocal regulation of phosphatidylcholine synthesis and H3K36 methylation programs metabolic adaptation.

  2022cites this paper
• Does chromatin function as a metabolite reservoir?

  2022cites this paper
• Acetyl-CoA regulates lipid metabolism and histone acetylation modification in cancer.

  2022cites this paper
• Oleic acid-related anti-inflammatory effects in force-stressed PdL fibroblasts are mediated by H3 lysine acetylation associated with altered IL10 expression

  2022cites this paper
• Chromatin as a metabolic organelle: Integrating the cellular flow of carbon with gene expression.

  2022cites this paper
• Nutrient regulation of the islet epigenome controls adaptive insulin secretion

  2019cites this paper