A split horseradish peroxidase for the detection of intercellular protein–protein interactions and sensitive visualization of synapses
Name
A split horseradish.pdf
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Author(s)
Yamagata, Masahito
Deerinck, Thomas J
Phan, Sébastien
Ellisman, Mark H
Sanes, Joshua R
Martell, Jeffrey Daniel
Kwa, Carolyn
Ting, Alice Y
Date Issued
May 2016
Journal
Nature Biotechnology
Publisher
Nature Publishing Group
Citation
Martell, Jeffrey D et al. “A Split Horseradish Peroxidase for the Detection of Intercellular Protein–protein Interactions and Sensitive Visualization of Synapses.” Nature Biotechnology 34.7 (2016): 774–780.
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 Chemistry
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
http://dx.doi.org/10.1038/nbt.3563
