ASF1 Binds to a Heterodimer of Histones H3 and H4:  A Two-Step Mechanism for the Assembly of the H3−H4 Heterotetramer on DNA

English, Christine M.; Maluf, Nasib K.; Tripet, Brian; Churchill, Mair E. A.; Tyler, Jessica K.

doi:10.1021/bi051333h

Cited by 120 publications

(126 citation statements)

References 56 publications

(102 reference statements)

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“…These structures have been very rewarding in that they provide intriguing insights into the mechanism of nucleosome disassembly. In vitro and in vivo evidence that Asf1 binds a heterodimer of H3/H4 (and not, as previously assumed, a (H3-H4) 2 tetramer) [51] [52] [53] were confirmed by x-ray crystallography, and the structural basis for these observations became immediately obvious. Asf1 binds the C-terminal α3-helix of H3, preventing the formation of the (H3-H4) 2 through the four-helix bundle (Figure 4).…”

Section: Chaperone -Histone Interactions and Implications For Nucleosmentioning

confidence: 69%

Histone chaperones in nucleosome eviction and histone exchange

Park

Luger

2008

Current Opinion in Structural Biology

172

143

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Section: Chaperone -Histone Interactions and Implications For Nucleosmentioning

confidence: 69%

Histone chaperones in nucleosome eviction and histone exchange

Park

Luger

2008

Current Opinion in Structural Biology

172

143

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“…Furthermore, we do not think that the influence of Asf1 on H3 acetylation levels could be because of any potential role for Asf1 in shielding histone H3 from deacetylation following its deposition onto the DNA because the crystal structure of Asf1 bound to H3/H4 (22) indicates that Asf1 must be removed from histones H3/H4 to enable interaction with histones H2A/H2B and the DNA within the nucleosome. Our biophysical and structural analyses have clearly shown that the binding of Asf1 to the histone H3/H4 heterodimer envelops the surface of H3 that would otherwise mediate formation of the H3/H4 heterotetramer (30). Upon deletion of ASF1, this H3-H3 interaction interface of the H3/H4 heterodimer is no longer shielded, and it is likely that the soluble H3/H4 in the cell would associate into H3/H4 heterotetramers prior to chromatin assembly.…”

Section: Asf1 Is Likely To Present the Newly Synthesized Freementioning

confidence: 91%

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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“…However, expectations for the H3-H4 tetramer split model revived in the past few years, after the discoveries that H3-H4 histones deposit onto chromatin as dimers rather than tetramers [28][29][30], and that the histone chaperone Asf1 blocks H3-H4 tetramer formation [31,32] and even disrupts pre-assembled H3-H4 tetramers to form H3-H4/Asf1 heterotrimers [32]. Although without direct evidence, these studies certainly offered a possibility for the H3-H4 tetramer splitting events.…”

Section: Bing Zhu and Danny Reinberg 437mentioning

confidence: 99%

Epigenetic inheritance: Uncontested?

Reinberg

2011

Cell Res

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"Epigenetics" is currently defined as "the inheritance of variation (-genetics) above and beyond (epi-) changes in the DNA sequence". Despite the fact that histones are believed to carry important epigenetic information, little is known about the molecular mechanisms of the inheritance of histone-based epigenetic information, including histone modifications and histone variants. Here we review recent progress and discuss potential models for the mitotic inheritance of histone modifications-based epigenetic information.

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ASF1 Binds to a Heterodimer of Histones H3 and H4: A Two-Step Mechanism for the Assembly of the H3−H4 Heterotetramer on DNA

Cited by 120 publications

References 56 publications

Histone chaperones in nucleosome eviction and histone exchange

Histone chaperones in nucleosome eviction and histone exchange

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

Epigenetic inheritance: Uncontested?

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