Evidence map›Paper›PMID 33767158›Full record

ArticleNature communications2021

The deubiquitinase Usp9x regulates PRC2-mediated chromatin reprogramming during mouse development.

Trisha A Macrae, Miguel Ramalho-Santos

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

7 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. mNature cell biology · 2023
    Article
  6. mbioRxiv : the preprint server for biology · 2023
    Article
  7. Review
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

2 authors at 1 institution in 2 countries.

Trisha A MacraeEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
Miguel Ramalho-SantosEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA. mrsantos@lunenfeld.ca.ORCID http://orcid.org/0000-0003-0177-5556
Mount Sinai Hospital · CA

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GERMAN, MICHAEL S · 2003 to 2019
$21.8M
Regulation of developmental potency by the transposon LINE1R01GM123556 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCMANUS, MICHAEL T · 2017 to 2020
$1.6M
Role of Chd1 in the transcriptional output and development of pluripotent cellsR01GM113014 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RAMALHO-SANTOS, MIGUEL · 2015 to 2018
$1.2M
Dissecting the developmental roles of the deubiquitinase Usp9xF30HD093116 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MACRAE, TRISHA A. · 2017 to 2020
$170k
CIHR 420231NICHD NIH HHS F30 HD093116NIDDK NIH HHS P30 DK063720NIGMS NIH HHS R01 GM113014NIGMS NIH HHS R01 GM123556NIGMS NIH HHS T32 GM007618
6 · The paper itself

Abstract

Pluripotent cells of the mammalian embryo undergo extensive chromatin rewiring to prepare for lineage commitment after implantation. Repressive H3K27me3, deposited by Polycomb Repressive Complex 2 (PRC2), is reallocated from large blankets in pre-implantation embryos to mark promoters of developmental genes. The regulation of this global redistribution of H3K27me3 is poorly understood. Here we report a post-translational mechanism that destabilizes PRC2 to constrict H3K27me3 during lineage commitment. Using an auxin-inducible degron system, we show that the deubiquitinase Usp9x is required for mouse embryonic stem (ES) cell self-renewal. Usp9x-high ES cells have high PRC2 levels and bear a chromatin and transcriptional signature of the pre-implantation embryo, whereas Usp9x-low ES cells resemble the post-implantation, gastrulating epiblast. We show that Usp9x interacts with, deubiquitinates and stabilizes PRC2. Deletion of Usp9x in post-implantation embryos results in the derepression of genes that normally gain H3K27me3 after gastrulation, followed by the appearance of morphological abnormalities at E9.5, pointing to a recurrent link between Usp9x and PRC2 during development. Usp9x is a marker of "stemness" and is mutated in various neurological disorders and cancers. Our results unveil a Usp9x-PRC2 regulatory axis that is critical at peri-implantation and may be redeployed in other stem cell fate transitions and disease states.

Indexed as

AnimalsCells, CulturedChromatinChromatin Assembly and DisassemblyFemaleHistonesMiceMice, Inbred C57BLMice, KnockoutMouse Embryonic Stem CellsPluripotent Stem CellsPolycomb Repressive Complex 2RNA InterferenceRNA, Small InterferingUbiquitin ThiolesteraseChromatinHistonesPolycomb Repressive Complex 2RNA, Small InterferingUbiquitin ThiolesteraseUsp9x protein, mouse

Identifiers

PMID33767158
PMCPMC7994559
OpenAlexW3136454659

What OpenQuestion holds

Textmetadata
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.