Structural basis for recognition of H3K56-acetylated histone H3-H4 by the chaperone Rtt106

Dan Su, Qi Hu, Qing Li, James R. Thompson, Gaofeng Cui, Ahmed Fazly, Brian A. Davies, Maria Victoria Botuyan, Zhiguo Zhang, Georges Mer

Research output: Contribution to journalArticle

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Abstract

Dynamic variations in the structure of chromatin influence virtually all DNA-related processes in eukaryotes and are controlled in part by post-translational modifications of histones. One such modification, the acetylation of lysine 56 (H3K56ac) in the amino-terminal α-helix (αN) of histone H3, has been implicated in the regulation of nucleosome assembly during DNA replication and repair, and nucleosome disassembly during gene transcription. In Saccharomyces cerevisiae, the histone chaperone Rtt106 contributes to the deposition of newly synthesized H3K56ac-carrying H3-H4 complex on replicating DNA, but it is unclear how Rtt106 binds H3-H4 and specifically recognizes H3K56ac as there is no apparent acetylated lysine reader domain in Rtt106. Here, we show that two domains of Rtt106 are involved in a combinatorial recognition of H3-H4. An N-terminal domain homodimerizes and interacts with H3-H4 independently of acetylation while a double pleckstrin-homology (PH) domain binds the K56-containing region of H3. Affinity is markedly enhanced upon acetylation of K56, an effect that is probably due to increased conformational entropy of the αN helix of H3. Our data support a mode of interaction where the N-terminal homodimeric domain of Rtt106 intercalates between the two H3-H4 components of the (H3-H4) 2 tetramer while two double PH domains in the Rtt106 dimer interact with each of the two H3K56ac sites in (H3-H4) 2. We show that the Rtt106-(H3-H4) 2 interaction is important for gene silencing and the DNA damage response.

Original languageEnglish (US)
Pages (from-to)104-109
Number of pages6
JournalNature
Volume483
Issue number7387
DOIs
StatePublished - Mar 1 2012

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Acetylation
Histones
Nucleosomes
Lysine
Histone Chaperones
DNA
Entropy
Gene Silencing
Post Translational Protein Processing
Eukaryota
DNA Replication
DNA Repair
DNA Damage
Chromatin
Saccharomyces cerevisiae
Genes
Pleckstrin Homology Domains

ASJC Scopus subject areas

  • General

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Structural basis for recognition of H3K56-acetylated histone H3-H4 by the chaperone Rtt106. / Su, Dan; Hu, Qi; Li, Qing; Thompson, James R.; Cui, Gaofeng; Fazly, Ahmed; Davies, Brian A.; Botuyan, Maria Victoria; Zhang, Zhiguo; Mer, Georges.

In: Nature, Vol. 483, No. 7387, 01.03.2012, p. 104-109.

Research output: Contribution to journalArticle

Su, D, Hu, Q, Li, Q, Thompson, JR, Cui, G, Fazly, A, Davies, BA, Botuyan, MV, Zhang, Z & Mer, G 2012, 'Structural basis for recognition of H3K56-acetylated histone H3-H4 by the chaperone Rtt106', Nature, vol. 483, no. 7387, pp. 104-109. https://doi.org/10.1038/nature10861
Su, Dan ; Hu, Qi ; Li, Qing ; Thompson, James R. ; Cui, Gaofeng ; Fazly, Ahmed ; Davies, Brian A. ; Botuyan, Maria Victoria ; Zhang, Zhiguo ; Mer, Georges. / Structural basis for recognition of H3K56-acetylated histone H3-H4 by the chaperone Rtt106. In: Nature. 2012 ; Vol. 483, No. 7387. pp. 104-109.
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AU - Fazly, Ahmed

AU - Davies, Brian A.

AU - Botuyan, Maria Victoria

AU - Zhang, Zhiguo

AU - Mer, Georges

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