English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Allele-specific expression changes dynamically during T cell activation in HLA and other autoimmune loci

Gutierrez-Arcelus, M., Baglaenko, Y., Arora, J., Hannes, S., Luo, Y., Amariuta, T., et al. (2020). Allele-specific expression changes dynamically during T cell activation in HLA and other autoimmune loci. Nature Genetics, 52(3), 247-253. doi:10.1038/s41588-020-0579-4.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0006-081A-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-081B-4
Genre: Journal Article

Files

show Files
hide Files
:
s41588-020-0579-4.pdf (Publisher version), 7MB
 
File Permalink:
-
Name:
s41588-020-0579-4.pdf
Description:
-
Visibility:
Private
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Gutierrez-Arcelus, Maria, Author
Baglaenko, Yuriy, Author
Arora, Jatin1, 2, Author              
Hannes, Susan, Author
Luo, Yang, Author
Amariuta, Tiffany, Author
Teslovich, Nikola, Author
Rao, Deepak A., Author
Ermann, Joerg, Author
Jonsson, A. Helena, Author
Navarrete, Cristina, Author
Rich, Stephen S., Author
Taylor, Kent D., Author
Rotter, Jerome I., Author
Gregersen, Peter K., Author
Esko, Tonu, Author
Brenner, Michael B., Author
Raychaudhuri, Soumya, Author
Consortium, NHLBI Trans-Omics for Precision Medicine (TOPMed), Author
Affiliations:
1IMPRS for Evolutionary Biology, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445639              
2Emmy Noether Research Group Evolutionary Immunogenomics, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_2616693              

Content

show
hide
Free keywords: -
 Abstract: Genetic studies have revealed that autoimmune susceptibility variants are over-represented in memory CD4+ T cell regulatory elements1–3. Understanding how genetic variation affects gene expression in different T cell physiological states is essential for deciphering genetic mechanisms of autoimmunity4,5. Here, we characterized the dynamics of genetic regulatory effects at eight time points during memory CD4+ T cell activation with high-depth RNA-seq in healthy individuals. We discovered widespread, dynamic allele-specific expression across the genome, where the balance of alleles changes over time. These genes were enriched fourfold within autoimmune loci. We found pervasive dynamic regulatory effects within six HLA genes. HLA-DQB1 alleles had one of three distinct transcriptional regulatory programs. Using CRISPR–Cas9 genomic editing we demonstrated that a promoter variant is causal for T cell–specific control of HLA-DQB1 expression. Our study shows that genetic variation in cis-regulatory elements affects gene expression in a manner dependent on lymphocyte activation status, contributing to the interindividual complexity of immune responses.

Details

show
hide
Language(s): eng - English
 Dates: 2020-01-132020-02-172020-03
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1038/s41588-020-0579-4
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Nature Genetics
  Other : Nature Genet.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: New York, NY : Nature America, Inc.
Pages: - Volume / Issue: 52 (3) Sequence Number: - Start / End Page: 247 - 253 Identifier: ISSN: 1061-4036
CoNE: https://pure.mpg.de/cone/journals/resource/954925598609