Quantitative Dynamics of the Link between Cellular Metabolism and Histone Acetylation

Evertts, Adam G.; Zee, Barry M.; DiMaggio, Peter A.; Gonzales-Cope, Michelle; Coller, Hilary A.; Garcia, Benjamin A.

doi:10.1074/jbc.m112.428318

Cited by 102 publications

(126 citation statements)

References 51 publications

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“…1c). To further evaluate the contribution of deacetylation reactions, including histone deacetylation, to acetate production, we cultured HCT116 cells in [ 13 C 6 ]-glucose containing media for 6 hours (hrs), which is thought to be sufficient to label histones with acetyl groups 22 , followed by incubation with the histone deacetylase inhibitor SAHA for an additional 1 hr (Fig. 1e).…”

Section: Resultsmentioning

confidence: 99%

De novo acetate production is coupled to central carbon metabolism in mammals

Liu

et al. 2018

Preprint

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In cases of nutritional excess, there is incomplete catabolism of a nutritional source and secretion of a waste product (overflow metabolism), such as the conversion of glucose to lactate (the Warburg Effect) in tumors. Here we report that excess glucose metabolism generates acetate, a key nutrient whose source has been unclear. Conversion of pyruvate, the product of glycolysis, to acetate occurs through two mechanisms: 1) coupling to reactive oxygen species (ROS), and 2) a neomorphic enzyme activity from keto acid dehydrogenases that enable it to function as a pyruvate decarboxylase. Furthermore, we demonstrate that glucose-derived acetate is sufficient to maintain acetyl-coenzyme A (Ac-CoA) pools and cell proliferation in certain limited metabolic environments such as during mitochondrial dysfunction or ATP citrate lyase (ACLY) deficiency. Thus, de novo acetate production is coupled to the activity of central carbon metabolism providing possible regulatory mechanisms and links to pathophysiology.peer-reviewed)

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Section: Resultsmentioning

confidence: 99%

De novo acetate production is coupled to central carbon metabolism in mammals

Liu

et al. 2018

Preprint

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“…HFF cells and 293T cells were cultured and maintained as described previously (33,34). Briefly, HFF and 293T cells were cultured in Dulbecco's modification of Eagle's medium (DMEM) with high glucose (Life Technologies, Inc.), supplemented with 10% fetal bovine serum (FBS) (Sigma).…”

Section: Methodsmentioning

confidence: 99%

“…Peptide sequences that were not analyzed in this study are in gray. The H3.1/2(27-40) peptide is in blue, and the H3.3 (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) peptide is in red. The line connecting the four acetylation marks on H4(2-16) peptide indicates only the four-ac was enriched on old H4 but not two-ac or three-ac (Table 1).…”

Section: Mass Spectrometry Provides a Powerful Tool To Study Dynamicsmentioning

confidence: 99%

“…For phosphorylated peptides that were not included in the synthetic peptide library, an average correction factor generated from all the peptides with the same histone backbone was used. For the histone H3.3 (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) peptide, the H1.4 (25)(26)(27)(28)(29)(30)(31)(32) peptide, and the K9M(9 -17) peptide, no correction factors were available, and thus no correction was performed.…”

Section: Nano-liquid Chromatography Electrospray Ionization Tandem Mamentioning

confidence: 99%

“…3B). In addition to HeLa cells, we examined the distribution of H3S10ph in two additional cell lines, 293T cells and the primary cell line human foreskin fibroblast (HFF) cells (33). Fig.…”

Section: Systematic Analysis Of the Distribution Of Histone Ptms Inmentioning

confidence: 99%

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Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells

Lin

Yuan

Han

et al. 2016

Journal of Biological Chemistry

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How histone post-translational modifications (PTMs) are inherited through the cell cycle remains poorly understood. Canonical histones are made in the S phase of the cell cycle. Combining mass spectrometry-based technologies and stable isotope labeling by amino acids in cell culture, we question the distribution of multiple histone PTMs on old versus new histones in synchronized human cells. We show that histone PTMs can be grouped into three categories according to their distributions. Most lysine mono-methylation and acetylation PTMs are either symmetrically distributed on old and new histones or are enriched on new histones. In contrast, most di-and tri-methylation PTMs are enriched on old histones, suggesting that the inheritance of different PTMs is regulated distinctly. Intriguingly, old and new histones are distinct in their phosphorylation status during early mitosis in the following three human cell types: HeLa, 293T, and human foreskin fibroblast cells. The mitotic hallmark H3S10ph is predominantly associated with old H3 at early mitosis and becomes symmetric with the progression of mitosis. This same distribution was observed with other mitotic phosphorylation marks, including H3T3/T6ph, H3.1/ 2S28ph, and H1.4S26ph but not S28/S31ph on the H3 variant H3.3. Although H3S10ph often associates with the neighboring Lys-9 di-or tri-methylations, they are not required for the asymmetric distribution of Ser-10 phosphorylation on the same H3 tail. Inhibition of the kinase Aurora B does not change the distribution despite significant reduction of H3S10ph levels. However, K9me2 abundance on the new H3 is significantly reduced after Aurora B inhibition, suggesting a cross-talk between H3S10ph and H3K9me2.In eukaryotes, histone proteins facilitate the packaging of DNA molecules. The DNA double helix wraps around histone octamers to form nucleosomes. A histone octamer contains two copies of each core histone H3, H4, H2A, and H2B. A 5th histone, histone H1, is associated with the linker DNA which lies between the nucleosomes. Canonical histone proteins are cell cycle-dependent and are produced in S phase (1, 2), whereas cell cycle-independent histone variants (e.g. H3.3) are synthesized throughout the cell cycle (3). Histone proteins carry numerous post-translational modifications (PTMs) 3 that are involved in multiple functions such as epigenetic regulation of transcription, DNA damage repair, and cell cycle progression (4, 5). To maintain lineage identity and to guide proper transcription, cells must replicate PTMs from old histones onto new histones at each cell division. Major efforts have been devoted to understanding how histones themselves are transmitted through the DNA replication fork in S phase (6). In principle, the newly deposited nucleosomes could contain entirely old or newly synthesized histone proteins, or a mixture of both. Accumulating evidence suggests that most H3/H4 tetramers remain intact, with the exception of some H3.3/H4 tetramers, indicating that nucleosomes should contain either new or ...

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The paradox of metabolism in quiescent stem cells

Coller

2019

FEBS Letters

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The shift between a proliferating and a nonproliferating state is associated with significant changes in metabolic needs. Proliferating cells tend to have higher metabolic rates, and their metabolic profiles facilitate biosynthesis, as compared to those of nondividing cells of the same sort. Recent studies have elucidated specific molecules that control metabolic changes while cells shift between proliferation and quiescence. Embryonic stem cells, which are rapidly proliferating, tend to have metabolic patterns that are similar to those of nonstem cells in a proliferative state. Moreover, although adult stem cells tend to be quiescent, their metabolic profiles have been reported in multiple organs to more closely resemble those of proliferating than those of nondividing cells in some respects. The findings raise questions about whether there are metabolic profiles that are required for stemness, and whether these profiles relate to the metabolic properties that may be required for quiescence. Here, we review the literature on how metabolism changes upon commitment to proliferation and compare the proliferating and nonproliferating metabolic states of differentiated cells and embryonic and adult stem cells.

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Quantitative Dynamics of the Link between Cellular Metabolism and Histone Acetylation

Cited by 102 publications

References 51 publications

De novo acetate production is coupled to central carbon metabolism in mammals

De novo acetate production is coupled to central carbon metabolism in mammals

Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells

The paradox of metabolism in quiescent stem cells

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