Fate of newly synthesized histones in G<sub>1</sub> and G<sub>0</sub> cells

Wu, Ruilian; Perry, Linda J.; Bonner, William M.

doi:10.1016/0014-5793(83)81070-9

Cited by 13 publications

(14 citation statements)

References 17 publications

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“…Thus, the concentration of free histone may not be immediately limiting DNA synthesis, but its level would still decrease as histone is incorporated into existing chromatin by replacement and turnover (50). However, the level of histone mRNA might be expected to rise more slowly when cells are treated with pleiotropic inhibitors or inhibitors of protein and DNA synthesis together than when treated with inhibitors of protein synthesis alone.…”

Section: Discussionmentioning

confidence: 99%

“…When the inhibitor of DNA synthesis is added first, the concentration of free histone would be elevated, causing the level of S-phase mRNA and the rate of S-phase histone synthesis to be depressed. When the inhibitor of protein synthesis is added later, histone protein synthesis would be further depressed due to the greatly lowered efficiency of translation, and the concentration of free histone would decrease as the histones still become incorporated into chromatin by replacement or turnover (50). The lowered free histone concentration soon becomes limiting for replication, effectively "uncoupling" the effects of the inhibitor of DNA synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…Wu et al (51) further showed that in G1 and Go cells in which DNA replication is absent, a significant amount of histone synthesis with distinguishable variant patterns was present; furthermore, these histones became incorporated into nucleosomes in the absence of replication (50). Thus, the free histone pool would be in a dynamic steady state, its level depending on the rate of histone synthesis on the one hand and the rate of utilization into chromatin in the other, whether or not DNA is being replicated.…”

Section: Discussionmentioning

confidence: 99%

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Interrelationships of protein and DNA syntheses during replication of mammalian cells.

Sariban¹,

Wu²,

Erickson³

et al. 1985

Mol. Cell. Biol.

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During the replication of chromatin, the syntheses of the histone protein and DNA components are closely coordinated but not totally linked. The interrelationships of total protein synthesis, histone protein synthesis, DNA synthesis, and mRNA levels have been investigated in Chinese hamster ovary cells subjekted to several different types of inhibitors in several different tefiporal combinations. The results from these studies and results reported elsewhere can be brought together into a consistent framework which combines the idea of autoregulation of histone biosynthesis as originaly proposed by W. B. Butler and G. C. Mueller (Biochim. Biophys. Acta 294:481-496, 1973] with the presence of basal histone synthesis and the effects of protein synthesis on L)NA synthesis. The proposed framework obviates the difficulties of Butler and Mueller's model and may have wider application in understanding the control of cell growth.Most histone synthesis in eucaryotic cells occurs coordinated with DNA synthesis during the S-phase period of the cell cycle and is inhibited when DNA synthesis is inhibited (27, 32); however, an appreciable amount of histone synthesis has been found to occur in the G1 portion of the cell cycle and the Go state when there is no DNA replication (49, 51, 52). Butler and Mueller (8) showed that the coordination between histone and DNA synthesis resulted from alterations in the level of histone mRNA. The level of translatable histone mRNA in exponentially growing cells was greatly decreased when they were treated with inhibitors of DNA synthesis, and this in turn resulted in the inhibition of histone protein synthesis. However, when total protein synthesis was inhibited by cycloheximide or puromycin at the same time that DNA synthesis was inhibited with hydroxyurea, translatable histone mRNA levels did not decrease. Subsequently, investigators in several laboratories, measuring the levels of histone mRNAs by using cloned histone genes (5,12,17,20,21,30,38,39,42,43), have substantiated and extended those results to show that the histone mRNA is rapidly degraded during the inhibition of DNA synthesis but protected from degradation when protein synthesis is also inhibited.To explain their own results, Butler and Mueller (8) proposed a model in which the histone not bound to chromatin inhibited the translation of its own mRNAs, and presented evidence that the level of free histone in the cytoplasm did increase after treatment of cells with hydroxyurea. Others have also found evidence for a small but measurable pool (25).The general idea of autoregulation of histone synthesis has persisted (17,40,43) DNA synthesis from histone mRNA levels. They proposed that a protein with a short half-life coupled the two processes; thus, it rapidly disappeared when protein synthesis was iphibited. Alternatively, Graves and Marzluff (17) proposed that changes in deoxynucleotide metabolism may be involved in the regulation of histone mRNA levels.All these reports have concentrated on studies of histone mkNA levels and ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Interrelationships of protein and DNA syntheses during replication of mammalian cells.

Sariban¹,

Wu²,

Erickson³

et al. 1985

Mol. Cell. Biol.

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show abstract

“…Most histones in dividing cells are canonical histone proteins expressed from tandem gene arrays during S phase and are deposited onto chromatin concurrent with DNA synthesis (20)(21)(22). In contrast, nonallelic sequence variants of core histones are constitutively expressed throughout the cell cycle from single-or low-copynumber genes and are incorporated into chromatin largely through replication-independent mechanisms (20,(23)(24)(25)(26). Major H2A variants include H2A.Z, H2A.X, and macroH2A that play specialized roles in transcription, the DNA damage response, and heterochromatin formation, respectively (20,27).…”

Section: Importancementioning

confidence: 99%

Canonical and Variant Forms of Histone H3 Are Deposited onto the Human Cytomegalovirus Genome during Lytic and Latent Infections

Albright

Kalejta

2016

J Virol

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Chromatin is the nucleoprotein complex that protects and compacts eukaryotic genomes. It is responsible for a large part of the epigenetic control of transcription. The genomes of DNA viruses such as human cytomegalovirus (HCMV) are devoid of histones within virions but are chromatinized and epigenetically regulated following delivery to the host cell nucleus. How chromatin is initially assembled on viral genomes and which variant forms of the core histone proteins are deposited are incompletely understood. We monitored the deposition of both ectopically expressed and endogenous histones H3.1 and H3.2 (collectively, H3.1/2) and H3.3 during lytic and latent HCMV infections. Here, we show that they are deposited on HCMV genomes during lytic and latent infections, suggesting similar mechanisms of viral chromatin assembly during the different infection types and indicating that both canonical and variant core histones may be important modulators of infecting viral genomes. We further show that association of both H3.1/2 and H3.3 occurs independent of viral DNA synthesis or de novo viral gene expression, implicating cellular factors and/or virion components in the formation of chromatin on virion-delivered genomes during both lytic and latent infections. IMPORTANCEIt is well established that infecting herpesvirus genomes are chromatinized upon entry into the host cell nucleus. Why or how this occurs is a mystery. It is important to know why they are chromatinized in order to better understand cellular pathogen recognition (DNA sensing) pathways and viral fate determinations (lytic or latent) and to anticipate how artificially modulating chromatinization may impact viral infections. It is important to know how the genomes are chromatinized in order to potentially modulate the process for therapeutic effect. Our work showing that HCMV genomes are loaded with canonical and variant H3 histones during both lytic and latent infections strengthens the hypothesis that chromatinization pathways are similar between the two infection types, implicates virion or cellular factors in this process, and exposes the possibility that histone variants, in addition to posttranslational modification, may impact viral gene expression. These revelations are important to understanding and intelligently intervening in herpesvirus infections.T he large genomes of eukaryotic cells must be highly compacted in order to fit within the restricted volume of the nucleus. To accomplish this, eukaryotic DNA is packaged into a repeating nucleoprotein structure known as chromatin, the basic subunit of which is the nucleosome (1, 2). The core nucleosome particle consists of approximately 146 bp of DNA wrapped nearly twice around a histone hetero-octamer consisting of two copies each of the four core histone proteins H2A, H2B, H3, and H4 (3). Nucleosomes are further compacted into higher-order chromatin fibers through the incorporation of the linker histone H1, other nonhistone proteins, and structural RNA components (4-6).Wrapping DNA in nucleoso...

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“…All four H2A variants are synthesized in quiescent and S-phase cells, but only H2A.X and H2A.Z are synthesized in G1 and G2 cells [30, 311. H3.3 is the only H3 variant synthesized in quiescent G1 and G2 cells, whereas H3.1 and H3.2 are synthesized predominantly in S-phase cells [4, 21, 30, 311. Recently, it has been reported that the pattern of histone-H3-variant synthesis switches when resting or quiescent T-lymphocytes are induced to synthesize DNA by the presence of phytohemagglutinin [33]. In contrast to core-histone synthesis during the S-phase, corehistone synthesis in the G1-, G2-, and GO-phase is com-* To whom offprint requests should be sent pletely resistant to treatment with hydroxyurea [29,30,331; however, the histones synthesized during the GO-and G1phase are stably incorporated into mononucleosomes soon after synthesis [32]. Finally, non-S-phase histone synthesis remains unaltered during UV-induced DNA repair [33].…”

Section: Introductionmentioning

confidence: 99%

Specific alterations in the pattern of histone-3 synthesis during conversion of human leukemic cells to terminally differentiated cells in culture

Pantazis

Bonner

1984

Differentiation

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Fate of newly synthesized histones in G₁ and G₀ cells

Cited by 13 publications

References 17 publications

Interrelationships of protein and DNA syntheses during replication of mammalian cells.

Interrelationships of protein and DNA syntheses during replication of mammalian cells.

Canonical and Variant Forms of Histone H3 Are Deposited onto the Human Cytomegalovirus Genome during Lytic and Latent Infections

Specific alterations in the pattern of histone-3 synthesis during conversion of human leukemic cells to terminally differentiated cells in culture

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Fate of newly synthesized histones in G1 and G0 cells

Cited by 13 publications

References 17 publications

Interrelationships of protein and DNA syntheses during replication of mammalian cells.

Interrelationships of protein and DNA syntheses during replication of mammalian cells.

Canonical and Variant Forms of Histone H3 Are Deposited onto the Human Cytomegalovirus Genome during Lytic and Latent Infections

Specific alterations in the pattern of histone-3 synthesis during conversion of human leukemic cells to terminally differentiated cells in culture

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Fate of newly synthesized histones in G₁ and G₀ cells