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Proc Natl Acad Sci U S A
2013 May 21;11021:8495-500. doi: 10.1073/pnas.1300126110.
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Heterochromatin protein Sir3 induces contacts between the amino terminus of histone H4 and nucleosomal DNA.
Wang F, Li G, Altaf M, Lu C, Currie MA, Johnson A, Moazed D.
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The regulated binding of effector proteins to the nucleosome plays a central role in the activation and silencing of eukaryotic genes. How this binding changes the properties of chromatin to mediate gene activation or silencing is not fully understood. Here we provide evidence that association of the budding yeast silent information regulator 3 (Sir3) silencing protein with the nucleosome induces a conformational change in the amino terminus of histone H4 that promotes interactions between the conserved H4 arginines 17 and 19 (R17 and R19) and nucleosomal DNA. Substitutions of H4R17 and R19 with alanine abolish silencing in vivo, but have little or no effect on binding of Sir3 to nucleosomes or histone H4 peptides in vitro. Furthermore, in both the previously reported crystal structure of the Sir3-bromo adjacent homology (BAH) domain bound to the Xenopus laevis nucleosome core particle and the crystal structure of the Sir3-BAH domain bound to the yeast nucleosome core particle described here, H4R17 and R19 make contacts with nucleosomal DNA rather than with Sir3. These results suggest that Sir3 binding generates a more stable nucleosome by clamping H4R17 and R19 to nucleosomal DNA, and raise the possibility that such induced changes in histone-DNA contacts play major roles in the regulation of chromatin structure.
Adams,
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
2010, Pubmed
Adams,
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
2010,
Pubmed Altaf,
Interplay of chromatin modifiers on a short basic patch of histone H4 tail defines the boundary of telomeric heterochromatin.
2007,
Pubmed Armache,
Structural basis of silencing: Sir3 BAH domain in complex with a nucleosome at 3.0 Å resolution.
2011,
Pubmed Braunstein,
Transcriptional silencing in yeast is associated with reduced nucleosome acetylation.
1993,
Pubmed Buchberger,
Sir3-nucleosome interactions in spreading of silent chromatin in Saccharomyces cerevisiae.
2008,
Pubmed Dai,
Probing nucleosome function: a highly versatile library of synthetic histone H3 and H4 mutants.
2008,
Pubmed Davey,
Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 a resolution.
2002,
Pubmed
,
Xenbase Ehrentraut,
Structural basis for the role of the Sir3 AAA+ domain in silencing: interaction with Sir4 and unmethylated histone H3K79.
2011,
Pubmed Emsley,
Features and development of Coot.
2010,
Pubmed Filion,
Systematic protein location mapping reveals five principal chromatin types in Drosophila cells.
2010,
Pubmed Fingerman,
A charge-based interaction between histone H4 and Dot1 is required for H3K79 methylation and telomere silencing: identification of a new trans-histone pathway.
2007,
Pubmed Grunstein,
Histone acetylation in chromatin structure and transcription.
1997,
Pubmed Hecht,
Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast.
1995,
Pubmed Huang,
Inhibition of homologous recombination by a cohesin-associated clamp complex recruited to the rDNA recombination enhancer.
2006,
Pubmed Imai,
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase.
2000,
Pubmed Jenuwein,
Re-SET-ting heterochromatin by histone methyltransferases.
2001,
Pubmed Johnson,
Genetic evidence for an interaction between SIR3 and histone H4 in the repression of the silent mating loci in Saccharomyces cerevisiae.
1990,
Pubmed Johnson,
Reconstitution of heterochromatin-dependent transcriptional gene silencing.
2009,
Pubmed Johnson,
Identification of a non-basic domain in the histone H4 N-terminus required for repression of the yeast silent mating loci.
1992,
Pubmed Kabsch,
XDS.
2010,
Pubmed Kayne,
Extremely conserved histone H4 N terminus is dispensable for growth but essential for repressing the silent mating loci in yeast.
1988,
Pubmed Klar,
MAR1-a Regulator of the HMa and HMalpha Loci in SACCHAROMYCES CEREVISIAE.
1979,
Pubmed Kouzarides,
Chromatin modifications and their function.
2007,
Pubmed Kruger,
Amino acid substitutions in the structured domains of histones H3 and H4 partially relieve the requirement of the yeast SWI/SNF complex for transcription.
1995,
Pubmed Lee,
A positive role for histone acetylation in transcription factor access to nucleosomal DNA.
1993,
Pubmed
,
Xenbase Li,
Nucleosomes facilitate their own invasion.
2004,
Pubmed
,
Xenbase Li,
The role of chromatin during transcription.
2007,
Pubmed Liou,
Assembly of the SIR complex and its regulation by O-acetyl-ADP-ribose, a product of NAD-dependent histone deacetylation.
2005,
Pubmed Longtine,
Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae.
1998,
Pubmed Luger,
Crystal structure of the nucleosome core particle at 2.8 A resolution.
1997,
Pubmed McCoy,
Phaser crystallographic software.
2007,
Pubmed Moazed,
Common themes in mechanisms of gene silencing.
2001,
Pubmed Moazed,
Silent information regulator protein complexes in Saccharomyces cerevisiae: a SIR2/SIR4 complex and evidence for a regulatory domain in SIR4 that inhibits its interaction with SIR3.
1997,
Pubmed Moazed,
Mechanisms for the inheritance of chromatin states.
2011,
Pubmed Moretti,
Evidence that a complex of SIR proteins interacts with the silencer and telomere-binding protein RAP1.
1994,
Pubmed Muthurajan,
Crystal structures of histone Sin mutant nucleosomes reveal altered protein-DNA interactions.
2004,
Pubmed Ng,
Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association.
2002,
Pubmed Ng,
Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation.
2003,
Pubmed Norris,
Compensatory interactions between Sir3p and the nucleosomal LRS surface imply their direct interaction.
2008,
Pubmed Onishi,
Role of the conserved Sir3-BAH domain in nucleosome binding and silent chromatin assembly.
2007,
Pubmed Osborne,
The establishment of gene silencing at single-cell resolution.
2009,
Pubmed Park,
A core nucleosome surface crucial for transcriptional silencing.
2002,
Pubmed Rigaut,
A generic protein purification method for protein complex characterization and proteome exploration.
1999,
Pubmed Rine,
Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae.
1987,
Pubmed Rudner,
A nonhistone protein-protein interaction required for assembly of the SIR complex and silent chromatin.
2005,
Pubmed Rusche,
The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae.
2003,
Pubmed Sampath,
Mutational analysis of the Sir3 BAH domain reveals multiple points of interaction with nucleosomes.
2009,
Pubmed Smith,
A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family.
2000,
Pubmed Strahl,
The language of covalent histone modifications.
2000,
Pubmed Takahashi,
Dot1 and histone H3K79 methylation in natural telomeric and HM silencing.
2011,
Pubmed Tanner,
Silent information regulator 2 family of NAD- dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose.
2000,
Pubmed Tanny,
Budding yeast silencing complexes and regulation of Sir2 activity by protein-protein interactions.
2004,
Pubmed van Leeuwen,
Dot1p modulates silencing in yeast by methylation of the nucleosome core.
2002,
Pubmed White,
Structure of the yeast nucleosome core particle reveals fundamental changes in internucleosome interactions.
2001,
Pubmed
,
Xenbase Winn,
Overview of the CCP4 suite and current developments.
2011,
Pubmed Xu,
Sir2 deacetylates histone H3 lysine 56 to regulate telomeric heterochromatin structure in yeast.
2007,
Pubmed Yang,
Insights into the impact of histone acetylation and methylation on Sir protein recruitment, spreading, and silencing in Saccharomyces cerevisiae.
2008,
Pubmed Zhang,
Essential and redundant functions of histone acetylation revealed by mutation of target lysines and loss of the Gcn5p acetyltransferase.
1998,
Pubmed
