Parsing the Interferon Transcriptional Network and Its Disease Associations
Name
Parsing the interferon.pdf
Size
2.15 MB
Format
Adobe PDF
Checksum (MD5)
526d120cf7f8f1c961d80f73e6fd2148
Author(s)
Mostafavi, Sara
Yoshida, Hideyuki
Moodley, Devapregasan
LeBoité, Hugo
Rothamel, Katherine
Raj, Towfique
Ye, Chun Jimmie
Chevrier, Nicolas
Zhang, Shen-Ying
Feng, Ting
Date Issued
January 2016
Journal
Cell
Publisher
Elsevier
Citation
Mostafavi, Sara et al. “Parsing the Interferon Transcriptional Network and Its Disease Associations.” Cell 164.3 (2016): 564–578.
Version
Author's final manuscript
Abstract
Type 1 interferon (IFN) is a key mediator of organismal responses to pathogens, eliciting prototypical “interferon signature genes” that encode antiviral and inflammatory mediators. For a global view of IFN signatures and regulatory pathways, we performed gene expression and chromatin analyses of the IFN-induced response across a range of immunocyte lineages. These distinguished ISGs by cell-type specificity, kinetics, and sensitivity to tonic IFN and revealed underlying changes in chromatin configuration. We combined 1,398 human and mouse datasets to computationally infer ISG modules and their regulators, validated by genetic analysis in both species. Some ISGs are controlled by Stat1/2 and Irf9 and the ISRE DNA motif, but others appeared dependent on non-canonical factors. This regulatory framework helped to interpret JAK1 blockade pharmacology, different clusters being affected under tonic or IFN-stimulated conditions, and the IFN signatures previously associated with human diseases, revealing unrecognized subtleties in disease footprints, as affected by human ancestry.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cell.2015.12.032
