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

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 dimermore » 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.« less

Authors:
; ; ; ; ; ; ; ; ;  [1]
  1. Mayo
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1037919
Resource Type:
Journal Article
Journal Name:
Nature
Additional Journal Information:
Journal Volume: 483; Journal Issue: 03, 2012
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ACETYLATION; AFFINITY; BIOCHEMISTRY; BIOLOGY; CHROMATIN; CLATHRATES; DEPOSITION; DIMERS; DNA; DNA DAMAGES; DNA REPLICATION; ENTROPY; GENES; HISTONES; LYSINE; MODIFICATIONS; MOLECULAR BIOLOGY; NUCLEOSOMES; REPAIR; SACCHAROMYCES CEREVISIAE; TRANSCRIPTION

Citation Formats

Su, Dan, Hu, Qi, Li, Qing, Thompson, James R, Cui, Gaofeng, Fazly, Ahmed, Davies, Brian A, Botuyan, Maria Victoria, Zhang, Zhiguo, and Mer, Georges. Structural basis for recognition of H3K56-acetylated histone H3-H4 by the chaperone Rtt106. United States: N. p., 2013. Web. doi: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. United States. 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, and Mer, Georges. 2013. "Structural basis for recognition of H3K56-acetylated histone H3-H4 by the chaperone Rtt106". United States. https://doi.org/10.1038/nature10861.
@article{osti_1037919,
title = {Structural basis for recognition of H3K56-acetylated histone H3-H4 by the chaperone Rtt106},
author = {Su, Dan and Hu, Qi and Li, Qing and Thompson, James R and Cui, Gaofeng and Fazly, Ahmed and Davies, Brian A and Botuyan, Maria Victoria and Zhang, Zhiguo and Mer, Georges},
abstractNote = {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.},
doi = {10.1038/nature10861},
url = {https://www.osti.gov/biblio/1037919}, journal = {Nature},
number = 03, 2012,
volume = 483,
place = {United States},
year = {Mon Apr 08 00:00:00 EDT 2013},
month = {Mon Apr 08 00:00:00 EDT 2013}
}