Modifications to histones immediately after synthesis

Jackson, Vaughn; Shires, A; Tanphaichitr, Nongnuj; Chalkley, Roger

doi:10.1016/0022-2836(76)90282-5

Cited by 203 publications

(131 citation statements)

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“…This pattern closely resembles that of acetylation of lysine 56 on newly synthesized H3 prior to chromatin assembly (15), suggesting that the S-phase peak of H3 Lys-9 acetylation that we observed also reflects the acetylation of newly synthesized H3. The fact that the H3 lysine 9 acetylation levels go down after S-phase indicates for the first time that the deposition-specific acetylation on the N-terminal tail of H3 is removed following replication-dependent chromatin assembly, as is the case for the deposition-specific acetylation marks on the N terminus of histone H4 (11). In contrast to the wild type cells, the peak of S-phase-specific H3 lysine 9 acetylation was absent from the asf1⌬ cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The N-terminal tails of the newly synthesized histones H3 and H4 are characteristically modified on specific residues prior to their deposition onto DNA and are termed deposition-specific modifications. For example, new histone H4 is generally acetylated on lysines 5 and 12 (10), but following deposition onto the DNA, the newly synthesized H4 is deacetylated over the next 30 -60 min (11), which is required for proper chromatin maturation (12). Newly synthesized histone H3 is also acetylated, although the target residues and pattern of acetylation vary between species.…”

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confidence: 99%

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The Histone Chaperone Anti-silencing Function 1 Stimulates the Acetylation of Newly Synthesized Histone H3 in S-phase

Adkins

Carson

English

et al. 2007

Journal of Biological Chemistry

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Anti-silencing function 1 (Asf1) is a highly conserved chaperone of histones H3/H4 that assembles or disassembles chromatin during transcription, replication, and repair. We have found that budding yeast lacking Asf1 has greatly reduced levels of histone H3 acetylated at lysine 9. Lysine 9 is acetylated on newly synthesized budding yeast histone H3 prior to its assembly onto newly replicated DNA. Accordingly, we found that the vast majority of H3 Lys-9 acetylation peaked in S-phase, and this S-phase peak of H3 lysine 9 acetylation was absent in yeast lacking Asf1. By contrast, deletion of ASF1 has no effect on the S-phase specific peak of H4 lysine 12 acetylation; another modification carried by newly synthesized histones prior to chromatin assembly. We show that Gcn5 is the histone acetyltransferase responsible for the S-phase-specific peak of H3 lysine 9 acetylation. Strikingly, overexpression of Asf1 leads to greatly increased levels of H3 on acetylation on lysine 56 and Gcn5-dependent acetylation on lysine 9. Analysis of a panel of Asf1 mutations that modulate the ability of Asf1 to bind to histones H3/H4 demonstrates that the histone binding activity of Asf1 is required for the acetylation of Lys-9 and Lys-56 on newly synthesized H3. These results demonstrate that Asf1 does not affect the stability of the newly synthesized histones per se, but instead histone binding by Asf1 promotes the efficient acetylation of specific residues of newly synthesized histone H3.The eukaryotic genome is packaged into a nucleoprotein structure known as chromatin. The basic repeating unit of chromatin, the nucleosome, is made up of 147 base pairs of DNA wrapped around a histone octamer (two molecules each of histone proteins H2A, H2B, H3, and H4) (1). Chromatin provides a formidable obstacle to the cellular machinery gaining access to the DNA. Indeed, it is becoming apparent that chromatin is a highly dynamic structure that tightly regulates all nuclear processes that use DNA as a substrate; including transcription, DNA replication, repair, and recombination (2-4). Thus, the mechanisms by which chromatin structures are made and modified are fundamental questions of broad interest.The entire eukaryotic genome is assembled into chromatin following DNA replication, and this occurs in a stepwise manner; a tetramer of histones H3/H4 is deposited first followed by two dimers of H2A/H2B on the outside of the tetramer. Histone-binding proteins, termed histone chaperones, mediate chromatin assembly. It is known that when this process is coupled to DNA replication in vitro, it is mediated by the histone H3/H4 chaperone chromatin assembly factor 1 (CAF-1) 2 (5) together with another H3/H4 chaperone termed anti-silencing function 1 (Asf1) (6). CAF-1 and Asf1 have also been shown to localize to the sites of DNA replication (7, 8), supporting a role in assembling chromatin following DNA replication in vivo. The fact that CAF-1 and Asf1 co-purify with the replicationspecific histone variant H3.1 from HeLa cells is further evidence that Asf1 ...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

The Histone Chaperone Anti-silencing Function 1 Stimulates the Acetylation of Newly Synthesized Histone H3 in S-phase

Adkins

Carson

English

et al. 2007

Journal of Biological Chemistry

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“…The acetylation of the N-terminal tails of newly synthesized histones is turned over very rapidly in human cells (4,5). Therefore, the apparent absence of H3 Lys-56 acetylation in human cells could merely reflect technical limitations in detecting the small fraction of total histones that carry the modification.…”

Section: Discussionmentioning

confidence: 99%

“…Lysine acetylation on histones is best characterized for its role in transcriptional regulation, but evidence for a crucial function during replication and DNA damage tolerance is accumulating (1)(2)(3). Indeed, newly synthesized histones that are deposited throughout the genome during replication are transiently acetylated at several lysine residues (4,5). These include sites of acetylation in the N-terminal tails of both histones H3 and H4 (6 -8).…”

mentioning

confidence: 99%

Regulation of Histone H3 Lysine 56 Acetylation in Schizosaccharomyces pombe

Xhemalçe

Miller

Driscoll

et al. 2007

Journal of Biological Chemistry

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In Saccharomyces cerevisiae, acetylation of lysine 56 (Lys-56) in the globular domain of histone H3 plays an important role in response to genotoxic agents that interfere with DNA replication. However, the regulation and biological function of this modification are poorly defined in other eukaryotes. Here we show that Lys-56 acetylation in Schizosaccharomyces pombe occurs transiently during passage through S-phase and is normally removed in G 2 . Genotoxic agents that cause DNA double strand breaks during replication elicit a delay in deacetylation of histone H3 Lys-56. In addition, mutant cells that cannot acetylate Lys-56 are acutely sensitive to genotoxic agents that block DNA replication. Moreover, we show that Spbc342.06cp, a previously uncharacterized open reading frame, encodes the functional homolog of S. cerevisiae Rtt109, and that this protein acetylates H3 Lys-56 both in vitro and in vivo. Altogether, our results indicate that both the regulation of histone H3 Lys-56 acetylation by its histone acetyltransferase and histone deacetylase and its role in the DNA damage response are conserved among two distantly related yeast model organisms.Histone acetylation corresponds to the covalent attachment of an acetyl group to a lysine residue. This modification is mediated by histone acetyltransferases (HATs) 7 and is reversible as the acetyl group can be removed through the action of histone deacetylases (HDACs). Lysine acetylation on histones is best characterized for its role in transcriptional regulation, but evidence for a crucial function during replication and DNA damage tolerance is accumulating (1-3). Indeed, newly synthesized histones that are deposited throughout the genome during replication are transiently acetylated at several lysine residues (4, 5). These include sites of acetylation in the N-terminal tails of both histones H3 and H4 (6 -8). Recently, two novel sites of acetylation in the globular domains of newly synthesized histone molecules were uncovered by mass spectrometry of Saccharomyces cerevisiae histones, lysine 91 (Lys-91) of histone H4 (9) and lysine 56 (Lys-56) of histone H3 (10 -15).H3 Lys-56 acetylation (H3 Lys-56-Ac) shows a particular link between DNA replication and DNA damage tolerance. In budding yeast, this modification occurs concomitantly with DNA replication as virtually all the newly synthesized histone H3 molecules deposited throughout the genome are Lys-56-acetylated, whereas in the G 2 /M-phase of the cell cycle the vast majority of H3 Lys-56 is deacetylated (11,(15)(16)(17). However, in response to DNA breaks during replication, histone H3 Lys-56 acetylation is maintained in a DNA damage checkpointdependent manner. In S. cerevisiae this modification plays a key role in surviving DNA damage as cells in which histone H3 cannot be acetylated at Lys-56 are acutely sensitive to genotoxic agents that interfere with DNA replication (10 -13).The deacetylation of H3 Lys-56 requires the Sir2-related HDACs Hst3 and Hst4 (16,17). Hst3 and Hst4 are cell cycles regulated with peak...

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“…Histone acetylation is catalyzed by histone acetyltransferases (HATs), a group of enzymes that transfer the acetyl group from the cofactor acetyl-Coenzyme A (acetyl-CoA) to the ε-amino group of lysine residues on histones (Marmorstein and Roth, 2001;Roth et al, 2001;Carrozza et al, 2003;Marmorstein, 2004). It was discovered years ago that newly-synthesized histones were acetylated and rapidly deacetylated following deposition (Ruiz-Carrillo et al, 1975;Jackson et al, 1976). It is only recently that we have begun to appreciate the function of acetylated newly-synthesized H3-H4.…”

Section: Multiple Acetylation Events Regulate Assembly Of Newly-synthmentioning

confidence: 99%

Histones, histone chaperones and nucleosome assembly

Burgess

Zhang

2010

Protein Cell

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Chromatin structure governs a number of cellular processes including DNA replication, transcription, and DNA repair. During DNA replication, chromatin structure including the basic repeating unit of chromatin, the nucleosome, is temporarily disrupted, and then reformed immediately after the passage of the replication fork. This coordinated process of nucleosome assembly during DNA replication is termed replication-coupled nucleosome assembly. Disruption of this process can lead to genome instability, a hallmark of cancer cells. Therefore, addressing how replication-coupled nucleosome assembly is regulated has been of great interest. Here, we review the current status of this growing field of interest, highlighting recent advances in understanding the regulation of this important process by the dynamic interplay of histone chaperones and histone modifications.

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Modifications to histones immediately after synthesis

Cited by 203 publications

References 22 publications

The Histone Chaperone Anti-silencing Function 1 Stimulates the Acetylation of Newly Synthesized Histone H3 in S-phase

The Histone Chaperone Anti-silencing Function 1 Stimulates the Acetylation of Newly Synthesized Histone H3 in S-phase

Regulation of Histone H3 Lysine 56 Acetylation in Schizosaccharomyces pombe

Histones, histone chaperones and nucleosome assembly

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