Repository logo
 

Highly disordered histone H1-DNA model complexes and their condensates.

Simple item page
cam.issuedOnline2018-10-09
dc.contributor.authorTurner, Abigail L
dc.contributor.authorWatson, Matthew
dc.contributor.authorWilkins, Oscar G
dc.contributor.authorCato, Laura
dc.contributor.authorTravers, Andrew
dc.contributor.authorThomas, Jean O
dc.contributor.authorStott, Katherine
dc.contributor.orcidStott, Katherine [0000-0002-4014-1188]
dc.date.accessioned2018-11-22T00:30:45Z
dc.date.available2018-11-22T00:30:45Z
dc.date.issued2018-11-20
dc.description.abstractDisordered proteins play an essential role in a wide variety of biological processes, and are often posttranslationally modified. One such protein is histone H1; its highly disordered C-terminal tail (CH1) condenses internucleosomal linker DNA in chromatin in a way that is still poorly understood. Moreover, CH1 is phosphorylated in a cell cycle-dependent manner that correlates with changes in the chromatin condensation level. Here we present a model system that recapitulates key aspects of the in vivo process, and also allows a detailed structural and biophysical analysis of the stages before and after condensation. CH1 remains disordered in the DNA-bound state, despite its nanomolar affinity. Phase-separated droplets (coacervates) form, containing higher-order assemblies of CH1/DNA complexes. Phosphorylation at three serine residues, spaced along the length of the tail, has little effect on the local properties of the condensate. However, it dramatically alters higher-order structure in the coacervate and reduces partitioning to the coacervate phase. These observations show that disordered proteins can bind tightly to DNA without a disorder-to-order transition. Importantly, they also provide mechanistic insights into how higher-order structures can be exquisitely sensitive to perturbation by posttranslational modifications, thus broadening the repertoire of mechanisms that might regulate chromatin and other macromolecular assemblies.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.32948
dc.identifier.eissn1091-6490
dc.identifier.issn0027-8424
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285594
dc.languageeng
dc.language.isoeng
dc.publisherProceedings of the National Academy of Sciences
dc.publisher.urlhttp://dx.doi.org/10.1073/pnas.1805943115
dc.subjectchromatin
dc.subjecthistone H1
dc.subjectintrinsic disorder
dc.subjectphase separation
dc.subjectphosphorylation
dc.subjectAnimals
dc.subjectChromatin
dc.subjectChromatin Assembly and Disassembly
dc.subjectDNA
dc.subjectDNA-Binding Proteins
dc.subjectHistones
dc.subjectHumans
dc.subjectMagnetic Resonance Spectroscopy
dc.subjectNucleic Acid Conformation
dc.subjectPhosphorylation
dc.subjectProtein Binding
dc.subjectProtein Conformation
dc.subjectProtein Processing, Post-Translational
dc.titleHighly disordered histone H1-DNA model complexes and their condensates.
dc.typeArticle
dcterms.dateAccepted2018-09-18
prism.endingPage11969
prism.issueIdentifier47
prism.publicationDate2018
prism.publicationNameProc Natl Acad Sci U S A
prism.startingPage11964
prism.volume115
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/N022181/1)
rioxxterms.licenseref.startdate2018-11
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1073/pnas.1805943115

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
STOTT_CH1_PNAS_rev_rev_v17_FINAL-merged.pdf
Size:
2.52 MB
Format:
Adobe Portable Document Format
Description:
Accepted version
Licence
http://www.rioxx.net/licenses/all-rights-reserved
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
DepositLicenceAgreementv2.1.pdf
Size:
150.9 KB
Format:
Adobe Portable Document Format
Download

Collections

Cambridge University Research Outputs