Evidence map›Paper›PMID 30940194›Full record

ArticleEpigenetics & chromatin2019

Citrullination of HP1γ chromodomain affects association with chromatin.

Meike Wiese, Andrew J Bannister, Srinjan Basu, Wayne Boucher, Kai Wohlfahrt, Maria A Christophorou, Michael L Nielsen, David Klenerman, Ernest D Laue, Tony Kouzarides

Open access · goldAbstract read
In one paragraph

Article in Epigenetics & chromatin, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 22 citations in OpenAlex.

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  6. Cells · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Meike WieseThe Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
Andrew J BannisterThe Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
Srinjan BasuDepartment of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK. sb451@cam.ac.uk.
Wayne BoucherDepartment of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.
Kai WohlfahrtDepartment of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.
Maria A ChristophorouInstitute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK.
Michael L NielsenDepartment of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200, Copenhagen, Denmark.
David KlenermanDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Ernest D LaueDepartment of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.
Tony KouzaridesThe Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK. t.kouzarides@gurdon.cam.ac.uk.ORCID 0000-0002-8918-4162
University of Cambridge · GBUniversity of Copenhagen · DKWellcome/MRC Cambridge Stem Cell Institute · GBWestern General Hospital · GB

Funding

Cancer Research UK 10827Cancer Research UK 17001Cancer Research UK 27321Cancer Research UK C6946/A24843Cancer Research UK RG17001Medical Research Council MC_PC_12009Medical Research Council MR/K015850/1Medical Research Council MR/M010082/1Medical Research Council MR/P019471/1Wellcome TrustWellcome Trust 206291/Z/17/ZWellcome Trust WT203144
6 · The paper itself

Abstract

backgroundStem cell differentiation involves major chromatin reorganisation, heterochromatin formation and genomic relocalisation of structural proteins, including heterochromatin protein 1 gamma (HP1γ). As the principal reader of the repressive histone marks H3K9me2/3, HP1 plays a key role in numerous processes including heterochromatin formation and maintenance.

resultsWe find that HP1γ is citrullinated in mouse embryonic stem cells (mESCs) and this diminishes when cells differentiate, indicating that it is a dynamically regulated post-translational modification during stem cell differentiation. Peptidylarginine deiminase 4, a known regulator of pluripotency, citrullinates HP1γ in vitro. This requires R38 and R39 within the HP1γ chromodomain, and the catalytic activity is enhanced by trimethylated H3K9 (H3K9me3) peptides. Mutation of R38 and R39, designed to mimic citrullination, affects HP1γ binding to H3K9me3-containing peptides. Using live-cell single-particle tracking, we demonstrate that R38 and R39 are important for HP1γ binding to chromatin in vivo. Furthermore, their mutation reduces the residence time of HP1γ on chromatin in differentiating mESCs.

conclusionCitrullination is a novel post-translational modification of the structural heterochromatin protein HP1γ in mESCs that is dynamically regulated during mESC differentiation. The citrullinated residues lie within the HP1γ chromodomain and are important for H3K9me3 binding in vitro and chromatin association in vivo.

Indexed as

CitrullinationAnimalsBinding SitesCell DifferentiationCell LineChromosomal Proteins, Non-HistoneHeterochromatinHistone CodeHistonesMiceMouse Embryonic Stem CellsMutationProtein-Arginine DeiminasesProtein BindingCbx3 protein, mouseChromosomal Proteins, Non-HistoneHeterochromatinHistonesProtein-Arginine DeiminasesChromatinCitrullinationStem cell differentiation

Identifiers

PMID30940194
PMCPMC6444592
OpenAlexW2944793447

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.