TY - JOUR
T1 - A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation
AU - Atianand, Maninjay K.
AU - Hu, Wenqian
AU - Satpathy, Ansuman T.
AU - Shen, Ying
AU - Ricci, Emiliano P.
AU - Alvarez-Dominguez, Juan R.
AU - Bhatta, Ankit
AU - Schattgen, Stefan A.
AU - McGowan, Jason D.
AU - Blin, Juliana
AU - Braun, Joerg E.
AU - Gandhi, Pallavi
AU - Moore, Melissa J.
AU - Chang, Howard Y.
AU - Lodish, Harvey F.
AU - Caffrey, Daniel R.
AU - Fitzgerald, Katherine A.
N1 - Funding Information:
We sincerely thank Zhaozhao Jiang and Kelly Army for animal care and technical help, Mona Motwani and Shruti Sharma for help with flow cytometry, Alicia Schep for NucleoATAC analysis, Rui Li for help during initial stages of ATAC-seq library preparation, and all members of the Fitzgerald laboratory as well as Susan Carpenter (UCSC) for their insightful comments. We thank Michael Karin (UCSD) for providing RNA samples, and Scott Schaffer and John Leszyck (UMass, Worcester) for mass spectrometry. This study was supported by American Heart Association grant (14POST18930001) to M.K.A., by NIH grant (P50-HG007735) to H.Y.C., by NIH grant (DK068348) to H.F.L., and by grants from the Kenneth Rainin Foundation, Lupus Research Institute (LRI), and NIH (AI067497) to K.A.F.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/6/16
Y1 - 2016/6/16
N2 - Long intergenic noncoding RNAs (lincRNAs) are important regulators of gene expression. Although lincRNAs are expressed in immune cells, their functions in immunity are largely unexplored. Here, we identify an immunoregulatory lincRNA, lincRNA-EPS, that is precisely regulated in macrophages to control the expression of immune response genes (IRGs). Transcriptome analysis of macrophages from lincRNA-EPS-deficient mice, combined with gain-of-function and rescue experiments, revealed a specific role for this lincRNA in restraining IRG expression. Consistently, lincRNA-EPS-deficient mice manifest enhanced inflammation and lethality following endotoxin challenge in vivo. lincRNA-EPS localizes at regulatory regions of IRGs to control nucleosome positioning and repress transcription. Further, lincRNA-EPS mediates these effects by interacting with heterogeneous nuclear ribonucleoprotein L via a CANACA motif located in its 3′ end. Together, these findings identify lincRNA-EPS as a repressor of inflammatory responses, highlighting the importance of lincRNAs in the immune system.
AB - Long intergenic noncoding RNAs (lincRNAs) are important regulators of gene expression. Although lincRNAs are expressed in immune cells, their functions in immunity are largely unexplored. Here, we identify an immunoregulatory lincRNA, lincRNA-EPS, that is precisely regulated in macrophages to control the expression of immune response genes (IRGs). Transcriptome analysis of macrophages from lincRNA-EPS-deficient mice, combined with gain-of-function and rescue experiments, revealed a specific role for this lincRNA in restraining IRG expression. Consistently, lincRNA-EPS-deficient mice manifest enhanced inflammation and lethality following endotoxin challenge in vivo. lincRNA-EPS localizes at regulatory regions of IRGs to control nucleosome positioning and repress transcription. Further, lincRNA-EPS mediates these effects by interacting with heterogeneous nuclear ribonucleoprotein L via a CANACA motif located in its 3′ end. Together, these findings identify lincRNA-EPS as a repressor of inflammatory responses, highlighting the importance of lincRNAs in the immune system.
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U2 - 10.1016/j.cell.2016.05.075
DO - 10.1016/j.cell.2016.05.075
M3 - Article
C2 - 27315481
AN - SCOPUS:84975225164
SN - 0092-8674
VL - 165
SP - 1672
EP - 1685
JO - Cell
JF - Cell
IS - 7
ER -