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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse NIH 3T3 fibroblasts were starved by serum depletion and subsequently restimulated by addition of serum. Histone acetylation and histone synthesis were studied from the beginning of starvation to the point where most of the cells were in S-phase utilizing electrophoretic and fluorographic techniques. We found that the major part of histone acetylation and histone synthesis occurs during S-phase but that also in the absence of DNA synthesis there are significant changes in the acetylation and synthesis rates of the core histones which occur during the first 6 hours of serum stimulation of quiescent cells, and between 24 and 48 hours of serum starvation.
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PMID:Histone acetylation and histone synthesis in mouse fibroblasts during quiescence and restimulation into S-phase. 201 Nov 18

Histone H1 is highly phosphorylated in transcriptionally active, amitotic macronuclei of Tetrahymena during vegetative growth. However, the level of H1 phosphorylation changes dramatically in response to different physiological conditions. H1 is hyperphosphorylated in response to heat shock and during prezygotic stages of conjugation. Conversely, H1 is largely dephosphorylated during prolonged starvation and during elimination of parental macronuclei during conjugation. Mapping of phosphorylation sites within H1 indicates that phosphorylation occurs at multiple sites in the amino-terminal portion of the molecule, predominantly at threonine residues. Two of these sites have been identified by compositional analyses and microsequencing of tryptic peptides. Interestingly, two major sites contain the sequence Thr-Pro-Val-Lys similar to that contained in the sites recognized by growth-associated histone kinase in other organisms. No new sites are detected during the hyperphosphorylation of H1 which occurs during heat shock or in early stages of conjugation, and no sites are preferentially dephosphorylated during starvation or later stages of conjugation. Therefore, changes in the overall level of H1 phosphorylation, as opposed to phosphorylation or dephosphorylation at particular sites, appear to be important in the regulation of chromatin structure under these physiological conditions. Further, since no cell division or DNA replication occurs under these conditions, changes in the level of H1 phosphorylation are best correlated to changes in gene expression during heat shock, starvation, and conjugation. We suggest that, at least in Tetrahymena, H1 hyperphosphorylation is used as a rapid and transient mechanism for the cessation of transcription under conditions of cellular stress.
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PMID:Characterization of phosphorylation sites in histone H1 in the amitotic macronucleus of Tetrahymena during different physiological states. 320 16

Histone mRNA was partially purified from mouse myeloma cells synchronized in S phase by isoleucine starvation. A cDNA was prepared that contained sequences complementary to all five mouse histone genes. This cDNA was used to screen a library of mouse DNA in lambda phage. The positive clones were screened by hybridization with sea urchin histone gene-specific probes to identify those clones that contained histone genes. Confirmation of this identification was obtained by hybridization with Drosophila histone genes. Two independent clusters of histone genes were isolated. One, MM531, contains regions hybridizing specifically to H3, H4, and H1 and the other, MM221, contains two regions hybridizing specifically to H3 and single regions complementary to H4, H2b, and H2a. They are not part of a simple repeating structure. The nucleotide sequence of the coding region of the H3 gene in MM531 has been determined. This gene could code for a variant H3 protein that has several amino acid substitutions not reported in other H3 proteins.
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PMID:Isolation of two clusters of mouse histone genes. 645 99

Histone synthesis and deposition into specific classes of nuclei has been investigated in starved and conjugating Tetrahymena. During starvation and early stages of conjugation (between 0 and 5 hr after opposite mating types are mixed), micronuclei selectively lose preexisting micronuclear-specific histones alpha, beta, gamma, and H3F. Of these histones, only alpha appears to accumulate in micronuclear chromatin through active synthesis and deposition during the mating process. Curiously, alpha is not observed (by stain or label) in young macronuclear anlagen (4C, 10 hr of conjugation). Thus, young macronuclear anlagen are missing all of the histones which are known to be specific to micronuclei of vegetative cells. By 14-16 hr of conjugation, we observe active synthesis and deposition of macronuclear-specific histones, hv1, hv2, and H1, into new macronuclear anlagen (8C). Thus macronuclear differentiation seems well underway by this time of conjugation. It is also in this time period (14-16 hr) that we first detect significant amounts of micronuclear-specific H1-like polypeptides beta and gamma in micronuclear extracts. These polypeptides do not seem to be synthesized during this period, which suggests that beta and gamma are derived from a precursor molecule(s). Since these micronuclear-specific histones do not appear in micronuclear chromatin until after other micronuclei have been selected to differentiate as macronuclei, we suspect that micronuclear differentiation is also an important process which occurs in 10-16 hr mating cells. Our results also suggest that proteolytic processing of micronuclear H3S into H3F (which occurs in a cell cycle dependent fashion during vegetative growth) is not operative during most if not all of conjugation. Thus micronuclei of mating cells contain only H3S which also seems consistent with the fact that some micronuclei differentiate into new macronuclei (micronuclear H3S is indistinguishable from macronuclear H3). Interestingly, the only H3 synthesized and deposited into the former macronucleus of mating cells is the relatively minor macronuclear-specific H3-like variant, hv2. These results demonstrate that significant histone rearrangements occur during conjugation in Tetrahymena in a manner consistent with the fact that during conjugation some micronuclei eventually differentiate into new macronuclei. Our results suggest that selective synthesis and deposition of specific histones (and histone variants) plays an important role in the nuclear differentiation process in Tetrahymena.
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PMID:Histone rearrangements accompany nuclear differentiation and dedifferentiation in Tetrahymena. 669 82

Histone acetyltransferases (HATs) such as Gcn5 play a role in transcriptional activation. However, the majority of constitutive genes show no requirement for GCN5, and even regulated genes, such as the yeast PHO5 gene, do not seem to be affected significantly by its absence under normal activation conditions. Here we show that even though the steady-state level of activated PHO5 transcription is not affected by deletion of GCN5, the rate of activation following phosphate starvation is significantly decreased. This delay in transcriptional activation is specifically due to slow chromatin remodeling of the PHO5 promoter, whereas the transmission of the phosphate starvation signal to the PHO5 promoter progresses at a normal rate. Chromatin remodeling is equally delayed in a galactose-inducible PHO5 promoter variant in which the Pho4 binding sites have been replaced by Gal4 binding sites. By contrast, activation of the GAL1 gene by galactose addition occurs with normal kinetics. Lack of the histone H4 N-termini leads to a similar delay in activation of the PHO5 promoter. These results indicate that one important contribution of HATs is to increase the rate of gene induction by accelerating chromatin remodeling, rather than to affect the final steady-state expression levels.
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PMID:Increasing the rate of chromatin remodeling and gene activation--a novel role for the histone acetyltransferase Gcn5. 1153 58

Histone modifications influence gene expression in complex ways. The RNA interference (RNAi) machinery can repress transcription by recruiting histone-modifying enzymes to chromatin, although it is not clear whether this is a general mechanism for gene silencing or whether it requires repeated sequences such as long terminal repeats (LTRs). We analyzed the global effects of the Clr3 and Clr6 histone deacetylases, the Clr4 methyltransferase, the zinc finger protein Clr1, and the RNAi proteins Dicer, RdRP, and Argonaute on the transcriptome of Schizosaccharomyces pombe (fission yeast). The clr mutants derepressed similar subsets of genes, many of which also became transcriptionally activated in cells that were exposed to environmental stresses such as nitrogen starvation. Many genes that were repressed by the Clr proteins clustered in extended regions close to the telomeres. Surprisingly few genes were repressed by both the silencing and RNAi machineries, with transcripts from centromeric repeats and Tf2 retrotransposons being notable exceptions. We found no correlation between repression by RNAi and proximity to LTRs, and the wtf family of repeated sequences seems to be repressed by histone deacetylation independent of RNAi. Our data indicate that the RNAi and Clr proteins show only a limited functional overlap and that the Clr proteins play more global roles in gene silencing.
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PMID:Global effects on gene expression in fission yeast by silencing and RNA interference machineries. 1563 61

Linker histone H1 is highly phosphorylated in normal growing Tetrahymena thermophila but becomes noticeably dephosphorylated in response to certain conditions such as prolonged starvation. Because phosphorylation of H1 has been associated with the regulation of gene expression, DNA repair, and other critical processes, we sought to use mass spectrometry-based approaches to obtain an in depth phosphorylation "signature" for this linker histone. Histone H1 from both growing and starved Tetrahymena was analyzed by nanoflow reversed-phase HPLC MS/MS following enzymatic digestions, propionic anhydride derivatization, and phosphopeptide enrichment via IMAC. We confirmed five phosphorylation sites identified previously and detected two novel sites of phosphorylation and two novel minor sites of acetylation. The sequential order of phosphorylation on H1 was deduced by using mass spectrometry to define the modified sites on phosphorylated H1 isoforms separated by cation-exchange chromatography. Relative levels of site-specific phosphorylation on H1 isolated from growing and starved Tetrahymena were obtained using a combination of stable isotopic labeling, IMAC, and tandem mass spectrometry.
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PMID:Comprehensive phosphoprotein analysis of linker histone H1 from Tetrahymena thermophila. 1683 17

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) conduct many critical functions through nonhistone substrates in metazoans, but only chromatin-associated nonhistone substrates are known in Saccharomyces cerevisiae. Using yeast proteome microarrays, we identified and validated many nonchromatin substrates of the essential nucleosome acetyltransferase of H4 (NuA4) complex. Among these, acetylation sites (Lys19 and 514) of phosphoenolpyruvate carboxykinase (Pck1p) were determined by tandem mass spectrometry. Acetylation at Lys514 was crucial for enzymatic activity and the ability of yeast cells to grow on nonfermentable carbon sources. Furthermore, Sir2p deacetylated Pck1p both in vitro and in vivo. Loss of Pck1p activity blocked the extension of yeast chronological life span caused by water starvation. In human hepatocellular carcinoma (HepG2) cells, human Pck1 acetylation and glucose production were dependent on TIP60, the human homolog of ESA1. Our findings demonstrate a regulatory function for the NuA4 complex in glucose metabolism and life span by acetylating a critical metabolic enzyme.
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PMID:Protein acetylation microarray reveals that NuA4 controls key metabolic target regulating gluconeogenesis. 1930 50

The plasticity of chromatin organization as chromosomes undergo a full compendium of transactions including DNA replication, recombination, chromatin compaction, and changes in transcription during a developmental program is unknown. We generated genome-wide maps of individual nucleosome organizational states, including positions and occupancy of all nucleosomes, and H3K9 acetylation and H3K4, K36, K79 tri-methylation, during meiotic spore development (gametogenesis) in Saccharomyces. Nucleosome organization was remarkably constant as the genome underwent compaction. However, during an acute meiotic starvation response, nucleosomes were repositioned to alter the accessibility of select transcriptional start sites. Surprisingly, the majority of the meiotic programs did not use this nucleosome repositioning, but was dominated by antisense control. Histone modification states were also remarkably stable, being abundant at specific nucleosome positions at three-quarters of all genes, despite most genes being rarely transcribed. Our findings suggest that, during meiosis, the basic features of genomic chromatin organization are essentially a fixed property of chromosomes, but tweaked in a restricted and program-specific manner.
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PMID:Stable and dynamic nucleosome states during a meiotic developmental process. 2151 15

Histone deacetylases (HDACs) are chromatin modifiers that alter gene expression but also exert a broad range of functions outside the nucleus by deacetylating non-histone target proteins. They gained growing attention for their implications in disease treatment, mainly through research using HDAC-inhibiting compounds. Understanding the effects of HDAC function and deregulation has therefore become an important focus for both basic and applied research. One of the described effects of HDAC inhibition is induction of autophagy. Autophagy is a ubiquitous process of recycling cellular components in response to starvation or stress and therefore crucial for cell homeostasis. Because of its role in managing anomalous protein overloads, autophagy is of great interest for neurodegenerative disease research. However, autophagy can also promote cell death, which puts it in the focus of cancer research. This review provides an overview of what we know of the impact of HDACs on the autophagy pathway and describes the fields where promising progress has been achieved, although one has to state that the work to illuminate the connections has just begun. Therefore, one focus is the effect of HDAC inhibition on autophagy in several types and models of cancer, which aims to find combinations of treatments that circumvent the ability of cancer cells to escape from cell death. Another recently emerged aspect is the direct involvement of the cytosolic deacetylase HDAC6 in autophagy progression, which is of great potential for revealing disease mechanisms in neurodegeneration.
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PMID:Interplay between histone deacetylases and autophagy--from cancer therapy to neurodegeneration. 2212 72


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