Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
A conformational switch in HP1 releases auto-inhibition to drive heterochromatin assembly.
Canzio D
,
Liao M
,
Naber N
,
Pate E
,
Larson A
,
Wu S
,
Marina DB
,
Garcia JF
,
Madhani HD
,
Cooke R
,
Schuck P
,
Cheng Y
,
Narlikar GJ
.
???displayArticle.abstract???
A hallmark of histone H3 lysine 9 (H3K9)-methylated heterochromatin, conserved from the fission yeast Schizosaccharomyces pombe to humans, is its ability to spread to adjacent genomic regions. Central to heterochromatin spread is heterochromatin protein 1 (HP1), which recognizes H3K9-methylated chromatin, oligomerizes and forms a versatile platform that participates in diverse nuclear functions, ranging from gene silencing to chromosome segregation. How HP1 proteins assemble on methylated nucleosomal templates and how the HP1-nucleosome complex achieves functional versatility remain poorly understood. Here we show that binding of the key S. pombe HP1 protein, Swi6, to methylated nucleosomes drives a switch from an auto-inhibited state to a spreading-competent state. In the auto-inhibited state, a histone-mimic sequence in one Swi6 monomer blocks methyl-mark recognition by the chromodomain of another monomer. Auto-inhibition is relieved by recognition of two template features, the H3K9 methyl mark and nucleosomal DNA. Cryo-electron-microscopy-based reconstruction of the Swi6-nucleosome complex provides the overall architecture of the spreading-competent state in which two unbound chromodomain sticky ends appear exposed. Disruption of the switch between the auto-inhibited and spreading-competent states disrupts heterochromatin assembly and gene silencing in vivo. These findings are reminiscent of other conditionally activated polymerization processes, such as actin nucleation, and open up a new class of regulatory mechanisms that operate on chromatin in vivo.
Bannister,
Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain.
2001, Pubmed
Bannister,
Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain.
2001,
Pubmed
Brasher,
The structure of mouse HP1 suggests a unique mode of single peptide recognition by the shadow chromo domain dimer.
2000,
Pubmed
Canzio,
Chromodomain-mediated oligomerization of HP1 suggests a nucleosome-bridging mechanism for heterochromatin assembly.
2011,
Pubmed
Cowieson,
Dimerisation of a chromo shadow domain and distinctions from the chromodomain as revealed by structural analysis.
2000,
Pubmed
Dawson,
JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin.
2009,
Pubmed
Eissenberg,
The HP1 protein family: getting a grip on chromatin.
2000,
Pubmed
Frank,
SPIDER and WEB: processing and visualization of images in 3D electron microscopy and related fields.
1996,
Pubmed
Frigon,
Magnesium-induced self-association of calf brain tubulin. II. Thermodynamics.
1975,
Pubmed
Grewal,
Heterochromatin revisited.
2007,
Pubmed
Hall,
Establishment and maintenance of a heterochromatin domain.
2002,
Pubmed
Huse,
The conformational plasticity of protein kinases.
2002,
Pubmed
Jacobs,
Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail.
2002,
Pubmed
Keller,
HP1(Swi6) mediates the recognition and destruction of heterochromatic RNA transcripts.
2012,
Pubmed
Lachner,
Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.
2001,
Pubmed
Lavigne,
Interaction of HP1 and Brg1/Brm with the globular domain of histone H3 is required for HP1-mediated repression.
2009,
Pubmed
LeRoy,
Heterochromatin protein 1 is extensively decorated with histone code-like post-translational modifications.
2009,
Pubmed
Li,
GPU-enabled FREALIGN: accelerating single particle 3D reconstruction and refinement in Fourier space on graphics processors.
2010,
Pubmed
Ludtke,
EMAN: semiautomated software for high-resolution single-particle reconstructions.
1999,
Pubmed
Luger,
Preparation of nucleosome core particle from recombinant histones.
1999,
Pubmed
,
Xenbase
Mendez,
The HP1a disordered C terminus and chromo shadow domain cooperate to select target peptide partners.
2011,
Pubmed
Mindell,
Accurate determination of local defocus and specimen tilt in electron microscopy.
2003,
Pubmed
Mullins,
How WASP-family proteins and the Arp2/3 complex convert intracellular signals into cytoskeletal structures.
2000,
Pubmed
Nakayama,
Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly.
2001,
Pubmed
Nielsen,
Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9.
2002,
Pubmed
Noma K,
Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries.
2001,
Pubmed
Pettersen,
UCSF Chimera--a visualization system for exploratory research and analysis.
2004,
Pubmed
Purcell,
Nucleotide pocket thermodynamics measured by EPR reveal how energy partitioning relates myosin speed to efficiency.
2011,
Pubmed
Rice,
A structural change in the kinesin motor protein that drives motility.
1999,
Pubmed
Richart,
Characterization of chromoshadow domain-mediated binding of heterochromatin protein 1α (HP1α) to histone H3.
2012,
Pubmed
Rougemaille,
Ers1, a rapidly diverging protein essential for RNA interference-dependent heterochromatic silencing in Schizosaccharomyces pombe.
2008,
Pubmed
Ruan,
Structural basis of the chromodomain of Cbx3 bound to methylated peptides from histone h1 and G9a.
2012,
Pubmed
Sadaie,
A chromodomain protein, Chp1, is required for the establishment of heterochromatin in fission yeast.
2004,
Pubmed
Sadaie,
Balance between distinct HP1 family proteins controls heterochromatin assembly in fission yeast.
2008,
Pubmed
Sampath,
Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly.
2007,
Pubmed
Simon,
Installation of site-specific methylation into histones using methyl lysine analogs.
2010,
Pubmed
Smothers,
The HP1 chromo shadow domain binds a consensus peptide pentamer.
2000,
Pubmed
Vistica,
Sedimentation equilibrium analysis of protein interactions with global implicit mass conservation constraints and systematic noise decomposition.
2004,
Pubmed
Wang,
Conservation of heterochromatin protein 1 function.
2000,
Pubmed
Yamada,
Functional domain structure of human heterochromatin protein HP1(Hsalpha): involvement of internal DNA-binding and C-terminal self-association domains in the formation of discrete dots in interphase nuclei.
1999,
Pubmed
Zhao,
Heterochromatin protein 1 binds to nucleosomes and DNA in vitro.
2000,
Pubmed
