Evidence map›Paper›PMID 34970970›Full record

ArticleHuman molecular genetics2022

Systematic identification of genomic elements that regulate FCGR2A expression and harbor variants linked with autoimmune disease.

Johanna Dahlqvist, Charles P Fulco, John P Ray, Thomas Liechti, Carl G de Boer, David J Lieb, Thomas M Eisenhaure, Jesse M Engreitz, Mario Roederer, Nir Hacohen

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

Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. EBV Triggers a Distinct Antiviral Response in HMC3 Cells.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. 3D genome alterations and editing in pathology.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Review
  9. Article
  10. Article
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 1 institution in 3 countries.

Johanna DahlqvistCenter for Cell Circuits, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.ORCID 0000-0002-6283-644X
Charles P FulcoCenter for Cell Circuits, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
John P RayCenter for Cell Circuits, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
Thomas LiechtiImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20814, USA.
Carl G de BoerKlarman Cell Observatory, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
David J LiebCenter for Cell Circuits, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
Thomas M EisenhaureCenter for Cell Circuits, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
Jesse M EngreitzCenter for Cell Circuits, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
Mario RoedererImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20814, USA.
Nir HacohenCenter for Cell Circuits, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
Broad Institute · US

Funding

Non-coding genetic variants that impact immune phenotypes and diseasesR01HG008131 · NHGRI · BROAD INSTITUTE, INC. · PI HACOHEN, NIR · 2015 to 2017
$2.6M
Systematic mapping and prediction of gene-enhancer connectionsR00HG009917 · NHGRI · STANFORD UNIVERSITY · PI ENGREITZ, JESSE M · 2020 to 2022
$796k
Systematic mapping and prediction of gene-enhancer connectionsK99HG009917 · NHGRI · BROAD INSTITUTE, INC. · PI ENGREITZ, JESSE M · 2018 to 2019
$65k
NHGRI NIH HHS K99 HG009917NHGRI NIH HHS R00 HG009917NHGRI NIH HHS R00HG009917NHGRI NIH HHS R01 HG008131
6 · The paper itself

Abstract

backgroundFCGR2A binds antibody-antigen complexes to regulate the abundance of circulating and deposited complexes along with downstream immune and autoimmune responses. Although the abundance of FCRG2A may be critical in immune-mediated diseases, little is known about whether its surface expression is regulated through cis genomic elements and non-coding variants. In the current study, we aimed to characterize the regulation of FCGR2A expression, the impact of genetic variation and its association with autoimmune disease.

methodsWe applied CRISPR-based interference and editing to scrutinize 1.7 Mb of open chromatin surrounding the FCGR2A gene to identify regulatory elements. Relevant transcription factors (TFs) binding to these regions were defined through public databases. Genetic variants affecting regulation were identified using luciferase reporter assays and were verified in a cohort of 1996 genotyped healthy individuals using flow cytometry.

resultsWe identified a complex proximal region and five distal enhancers regulating FCGR2A. The proximal region split into subregions upstream and downstream of the transcription start site, was enriched in binding of inflammation-regulated TFs, and harbored a variant associated with FCGR2A expression in primary myeloid cells. One distal enhancer region was occupied by CCCTC-binding factor (CTCF) whose binding site was disrupted by a rare genetic variant, altering gene expression.

conclusionsThe FCGR2A gene is regulated by multiple proximal and distal genomic regions, with links to autoimmune disease. These findings may open up novel therapeutic avenues where fine-tuning of FCGR2A levels may constitute a part of treatment strategies for immune-mediated diseases.

Indexed as

Autoimmune DiseasesEnhancer Elements, GeneticReceptors, IgGBinding SitesGenomicsGenotypeHumansFCGR2A protein, humanReceptors, IgG

Identifiers

PMID34970970
PMCPMC9239749
OpenAlexW4205317232

What OpenQuestion holds

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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.