Insights into the Role of Histone H3 and Histone H4 Core Modifiable Residues in <i>Saccharomyces cerevisiae</i>

Hyland, Edel M.; Cosgrove, Michael S.; Molina, Henrik; Wang, Dongxia; Pandey, Akhilesh; Cottee, Robert J.; Boeke, Jef D.

doi:10.1128/mcb.25.22.10060-10070.2005

Cited by 219 publications

(222 citation statements)

References 55 publications

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“…DNA repair also appears dependent on H3-K115 and/or H3-K122 acetylation. H3-K115Q increases sensitivity to hydroxyurea, whereas H3-K115R does not (23). Moreover, H3-K115A, H3-K122A, and H3-K122Q were all shown to be highly sensitive to Zeocin, a DNA double strand break mimetic (24).…”

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confidence: 97%

“…H3-K115R, which mimics constitutively unacetylated lysine, exhibits wild type silencing in both regions. However, H3-K122R exhibits wild type silencing in ribosomal DNA but reduced silencing in telomeres (23). Another study showed that H3-K115A and H3-K122A separately displayed reduced expression of the PHO5 gene in budding yeast, whereas H3-K122A exhibited wild type expression (24).…”

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confidence: 99%

“…Replacing H3-K115Q and H3-K122Q in yeast reduces transcriptional silencing at ribosomal DNA and telomeres (23). H3-K115R, which mimics constitutively unacetylated lysine, exhibits wild type silencing in both regions.…”

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Acetylation of Histone H3 at the Nucleosome Dyad Alters DNA-Histone Binding

Manohar¹,

Mooney²,

North³

et al. 2009

Journal of Biological Chemistry

123

153

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Histone post-translational modifications are essential for regulating and facilitating biological processes such as RNA transcription and DNA repair. Fifteen modifications are located in the DNA-histone dyad interface and include the acetylation of H3-K115 (H3-K115Ac) and H3-K122 (H3-K122Ac), but the functional consequences of these modifications are unknown. We have prepared semisynthetic histone H3 acetylated at Lys-115 and/or Lys-122 by expressed protein ligation and incorporated them into single nucleosomes. Competitive reconstitution analysis demonstrated that the acetylation of H3-K115 and H3-K122 reduces the free energy of histone octamer binding. Restriction enzyme kinetic analysis suggests that these histone modifications do not alter DNA accessibility near the sites of modification. However, acetylation of H3-K122 increases the rate of thermal repositioning. Remarkably, Lys 3 Gln substitution mutations, which are used to mimic Lys acetylation, do not fully duplicate the effects of the H3-K115Ac or H3-K122Ac modifications. Our results are consistent with the conclusion that acetylation in the dyad interface reduces DNA-histone interaction(s), which may facilitate nucleosome repositioning and/or assembly/disassembly.All eukaryotic genomes are organized into strings of nucleosomes, where 147 bp of DNA are tightly wrapped around a histone protein octamer (1). Many biological processes are dependent on DNA-protein interactions. However, access to DNA-binding sites is often restricted by the nucleosome structure. Alterations in nucleosome structure, dynamics, and positioning have been hypothesized to play a gatekeeper role in regulating biological processes such as DNA replication, repair, and transcription (2).The post-translational modification (PTM) 3 of core histones (3) plays a central role in regulating the biological processing of eukaryotic genomes. Until recently, known histone PTMs were almost exclusively located on the unstructured histone tail regions, which extend from the structured core of the nucleosomes. PTMs in the histone tails can function to directly alter nucleosome (4 -6) and/or chromatin structure and stability (7,8) and function as protein-binding sites (9) in the "histone code" model (10).During the past 5 years over 30 additional histone PTMs were identified within structured regions of the nucleosome (11-13). Many of these modifications are buried within the nucleosome core and thus are not readily accessible for protein binding. Fifteen of these histone PTMs are located in the DNAhistone interface, where the histone octamer contacts the phosphate backbone of the wrapped DNA (14). Studies have suggested that only mild structural perturbations occur in coremodified nucleosomes, which implies that modifications buried beneath the DNA are unlikely to provide a protein-binding site (15). This has led to two additional models for the function of nucleosome core PTMs.Modifications such as Lys acetylation that reduce the positive charge of the histone octamer surface may reduce the bindi...

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Acetylation of Histone H3 at the Nucleosome Dyad Alters DNA-Histone Binding

Manohar¹,

Mooney²,

North³

et al. 2009

Journal of Biological Chemistry

123

153

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“…1,2 Six independent research groups recently reported the discovery of lysine 56 as a novel site of histone H3 acetylation in the budding yeast Saccharomyces cerevisiae. [3][4][5][6][7][8] K56 acetylation has also been observed in the fission yeast Schizosaccharomyces pombe, 6 which is evolutionarily very distant from S. cerevisiae. 9 Based on mass spectrometry, K56 acetylation occurs in Plasmodium falciparum (A. Salcedo and H. Stunnenberg, in preparation) and the modification has also been reported in Drosophila.…”

Section: Introductionmentioning

confidence: 99%

Histone H3 Lysine 56 Acetylation: A New Twist in the Chromosome Cycle

Özdemir¹,

Masumoto²,

Fitzjohn³

et al. 2006

Cell Cycle

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Several recent reports have identified lysine 56 (K56) as a novel site of acetylation in yeast histone H3. K56 acetylation is predicted to disrupt some of the histone-DNA interactions at the entry and exit points of the nucleosome core particle. This modification occurs in virtually all the newly synthesised histones that are deposited into chromatin during S-phase. Cells with mutations that block K56 acetylation show increased genome instability and hypersensitivity to genotoxic agents that interfere with replication. Removal of K56 acetylation takes place in the G 2 /M phase of the cell cycle and is dependent upon Hst3 and Hst4, two proteins that are related to the NAD + -dependent histone deacetylase Sir2. In response to DNA damage checkpoint activation during S-phase, expression of Hst3/Hst4 is delayed to extend the window of opportunity in which K56 acetylation can act in the DNA damage response. The high abundance of histone H3 K56 acetylation, its regulation and strategic location in the nucleosome core particle raise a number of fascinating issues that we discuss here.

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“…Additionally, in eukaryotic genetic model organisms, like Saccharomyces cerevisiae, a model that allows for direct mutations of histones in vivo, the majority of histone N-terminal tail point mutants have been demonstrated to be completely viable despite apparent evolutionary pressures to conserve near-invariant histone amino-acid sequences (Hyland et al, 2005;Dai et al, 2008). Although specific core amino acids located at the H3/H4 histone-fold motif have been shown to be important for aspects of transcriptional silencing in yeast (this core is centered around lysine 79 of H3 and may be important to nucleosomal stability) (Park et al, 2002), these data indicate a high level of functional redundancy in histone modifications that must be considered.…”

Section: Reconciling the Dangers Of Hyper-enthusiasm With Cautious Inmentioning

confidence: 99%

Histone Regulation in the CNS: Basic Principles of Epigenetic Plasticity

Maze

Noh

Allis

2012

Neuropsychopharmacol

115

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Postmitotic neurons are subject to a vast array of environmental influences that require the nuclear integration of intracellular signaling events to promote a wide variety of neuroplastic states associated with synaptic function, circuit formation, and behavioral memory. Over the last decade, much attention has been paid to the roles of transcription and chromatin regulation in guiding fundamental aspects of neuronal function. A great deal of this work has centered on neurodevelopmental and adulthood plasticity, with increased focus in the areas of neuropharmacology and molecular psychiatry. Here, we attempt to provide a broad overview of chromatin regulation, as it relates to central nervous system (CNS) function, with specific emphasis on the modes of histone posttranslational modifications, chromatin remodeling, and histone variant exchange. Understanding the functions of chromatin in the context of the CNS will aid in the future development of pharmacological therapeutics aimed at alleviating devastating neurological disorders.

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Insights into the Role of Histone H3 and Histone H4 Core Modifiable Residues in Saccharomyces cerevisiae

Cited by 219 publications

References 55 publications

Acetylation of Histone H3 at the Nucleosome Dyad Alters DNA-Histone Binding

Acetylation of Histone H3 at the Nucleosome Dyad Alters DNA-Histone Binding

Histone H3 Lysine 56 Acetylation: A New Twist in the Chromosome Cycle

Histone Regulation in the CNS: Basic Principles of Epigenetic Plasticity

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