Evidence map›Paper›PMID 33770495›Full record

ArticleStem cell reports2021

Inaccessible LCG Promoters Act as Safeguards to Restrict T Cell Development to Appropriate Notch Signaling Environments.

Suzanne Furuyama, Qian Vicky Wu, Barbara Varnum-Finney, Richard Sandstrom, Wouter Meuleman, John A Stamatoyannopoulos, Irwin D Bernstein

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.1field-weighted citation impact, top 58% 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

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

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

7 authors at 3 institutions in 1 country.

Suzanne FuruyamaClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Qian Vicky WuClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Barbara Varnum-FinneyClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Richard SandstromAltius Institute for Biomedical Sciences, Seattle, WA 98121, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Wouter MeulemanAltius Institute for Biomedical Sciences, Seattle, WA 98121, USA.
John A StamatoyannopoulosAltius Institute for Biomedical Sciences, Seattle, WA 98121, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Department of Medicine, Division of Oncology, University of Washington, Seattle, WA 98195, USA.
Irwin D BernsteinClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Washington, Seattle, WA 98195, USA. Electronic address: ibernste@fredhutch.org.
Fred Hutch Cancer Center · USAltius Institute for Biomedical Sciences · USUniversity of Washington · US

Funding

Expansion of Cardiac and Hematopoietic Pregenitors by Wnt and NotchU01HL100395 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BERNSTEIN, IRWIN D, MOON, RANDALL TODD · 2009 to 2015
$8.4M
Novel regulation of Notch-induced HSPC expansionR01DK110563 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BERNSTEIN, IRWIN D · 2017 to 2020
$1.6M
NHLBI NIH HHS U01 HL100395NIDDK NIH HHS R01 DK110563
6 · The paper itself

Abstract

T cell development is restricted to the thymus and is dependent on high levels of Notch signaling induced within the thymic microenvironment. To understand Notch function in thymic restriction, we investigated the basis for target gene selectivity in response to quantitative differences in Notch signal strength, focusing on the chromatin architecture of genes essential for T cell differentiation. We find that high Notch signal strength is required to activate promoters of known targets essential for T cell commitment, including Il2ra, Cd3ε, and Rag1, which feature low CpG content (LCG) and DNA inaccessibility in hematopoietic stem progenitor cells. Our findings suggest that promoter DNA inaccessibility at LCG T lineage genes provides robust protection against stochastic activation in inappropriate Notch signaling contexts, limiting T cell development to the thymus.

Indexed as

Signal TransductionAnimalsCpG IslandsDeoxyribonuclease IDNAMiceMice, Inbred C57BLPromoter Regions, GeneticReceptors, NotchT-LymphocytesDeoxyribonuclease IDNAReceptors, NotchDNA accessibilityLCG promotersNotchT cell development

Identifiers

PMID33770495
PMCPMC8072033
OpenAlexW3139109110

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.