CD4 expression in effector T cells depends on DNA demethylation over a developmentally established stimulus-responsive element

Athmane Teghanemt; Priyanjali Pulipati; Kara Misel-Wuchter; Kenneth Day; Matthew S Yorek; Ren Yi; Henry L Keen; Christy Au; Thorsten Maretzky; Prajwal Gurung; Dan R Littman; Priya D Issuree

doi:10.1038/s41467-022-28914-4

Back

CD4 expression in effector T cells depends on DNA demethylation over a developmentally established stimulus-responsive element

Journal article

Open access

Peer reviewed

CD4 expression in effector T cells depends on DNA demethylation over a developmentally established stimulus-responsive element

Athmane Teghanemt, Priyanjali Pulipati, Kara Misel-Wuchter, Kenneth Day, Matthew S Yorek, Ren Yi, Henry L Keen, Christy Au, Thorsten Maretzky, Prajwal Gurung, …

Nature communications, Vol.13(1), pp.1477-1477

03/18/2022

DOI: 10.1038/s41467-022-28914-4

PMCID: PMC8933563

PMID: 35304452

Files and links (1)

url

https://doi.org/10.1038/s41467-022-28914-4View

Published (Version of record) Open Access

Abstract

The epigenetic patterns that are established during early thymic development might determine mature T cell physiology and function, but the molecular basis and topography of the genetic elements involved are not fully known. Here we show, using the Cd4 locus as a paradigm for early developmental programming, that DNA demethylation during thymic development licenses a novel stimulus-responsive element that is critical for the maintenance of Cd4 gene expression in effector T cells. We document the importance of maintaining high CD4 expression during parasitic infection and show that by driving transcription, this stimulus-responsive element allows for the maintenance of histone H3K4me3 levels during T cell replication, which is critical for preventing de novo DNA methylation at the Cd4 promoter. A failure to undergo epigenetic programming during development leads to gene silencing during effector T cell replication. Our study thus provides evidence of early developmental events shaping the functional fitness of mature effector T cells.

CD4-Positive T-Lymphocytes - metabolism

DNA Demethylation

DNA Methylation

Promoter Regions, Genetic - genetics

Details

Title: Subtitle: CD4 expression in effector T cells depends on DNA demethylation over a developmentally established stimulus-responsive element
Creators: Athmane Teghanemt - University of Iowa
Priyanjali Pulipati - University of Iowa
Kara Misel-Wuchter - Roy J. and Lucille A. Carver College of Medicine
Kenneth Day - Zymo Research Corporation, Irvine, CA, USA.
Matthew S Yorek - Roy J. and Lucille A. Carver College of Medicine
Ren Yi - New York University
Henry L Keen - University of Iowa
Christy Au - New York University
Thorsten Maretzky - Roy J. and Lucille A. Carver College of Medicine
Prajwal Gurung - University of Iowa
Dan R Littman - New York University
Priya D Issuree - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: Nature communications, Vol.13(1), pp.1477-1477
DOI: 10.1038/s41467-022-28914-4
PMID: 35304452
PMCID: PMC8933563
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Grant note: Howard Hughes Medical Institute P30 CA016087 / NCI NIH HHS
Language: English
Date published: 03/18/2022
Academic Unit: Infectious Diseases; Stead Family Department of Pediatrics; Pathology; Internal Medicine; Iowa Institute of Human Genetics
Record Identifier: 9984359880602771

Metrics

27 Record Views

7 Times Cited - Web of Science

See more details