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231225s2018 xx |||||o 00| ||eng c |
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|a 10.1016/j.clim.2018.08.011
|2 doi
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|a pubmed24n0959.xml
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|e rakwb
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|a eng
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| 100 |
1 |
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|a Kelly, Maurer
|e verfasserin
|4 aut
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| 245 |
1 |
0 |
|a Transposable element dysregulation in systemic lupus erythematosus and regulation by histone conformation and Hsp90
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| 264 |
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|c 2018
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| 336 |
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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| 500 |
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|a Date Completed 07.10.2019
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|a Date Revised 01.12.2019
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a Copyright © 2018 Elsevier Inc. All rights reserved.
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|a Systemic lupus erythematosus (SLE) represents an autoimmune disease in which activation of the type I interferon pathway leads to dysregulation of tolerance and the generation of autoantibodies directed against nuclear constituents. The mechanisms driving the activation of the interferon pathway in SLE have been the subject of intense investigation but are still incompletely understood. Transposable elements represent an enormous source of RNA that could potentially stimulate the cell intrinsic RNA-recognition pathway, leading to upregulation of interferons. We used RNA-seq to define transposable element families and subfamilies in three cell types in SLE and found diverse effects on transposable element expression in the three cell types and even within a given family of transposable elements. When potential mechanisms were examined, we found that Hsp90 inhibition could drive increased expression of multiple type of transposable elements. Both direct inhibition and the delivery of a heat shock itself, which redirects heat shock regulators (including Hsp90) off of basal expression promoters and onto heat shock-responsive promoters, led to increased transposable element expression. This effect was amplified by the concurrent delivery of a histone deacetylase inhibitor. We conclude that transposable elements are dysregulated in SLE and there are tissue-specific effects and locus-specific effects. The magnitude of RNAs attributable to transposable elements makes their dysregulation of critical interest in SLE where transposable element RNA complexed with proteins has been shown to drive interferon expression
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|a Journal Article
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|a Research Support, N.I.H., Extramural
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|a Research Support, Non-U.S. Gov't
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| 650 |
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4 |
|a Adar
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| 650 |
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|a Epigenetics
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|a Heat shock
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|a Histone deacetylase inhibitor
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| 650 |
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|a Lupus
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| 650 |
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4 |
|a RNaseL
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| 650 |
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|a DNA Transposable Elements
|2 NLM
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| 650 |
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|a HSP90 Heat-Shock Proteins
|2 NLM
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| 650 |
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7 |
|a Histone Deacetylase Inhibitors
|2 NLM
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| 650 |
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|a Histones
|2 NLM
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| 650 |
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|a Immunologic Factors
|2 NLM
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| 650 |
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|a Interferon Inducers
|2 NLM
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| 650 |
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|a Interferon-alpha
|2 NLM
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| 650 |
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|a Interferon-beta
|2 NLM
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| 650 |
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7 |
|a 77238-31-4
|2 NLM
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| 650 |
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|a Poly I-C
|2 NLM
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| 650 |
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7 |
|a O84C90HH2L
|2 NLM
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| 700 |
1 |
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|a Lihua, Shi
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zhe, Zhang
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Li, Song
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yoselin, Paucar
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Michelle, Petri
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Sullivan Kathleen, E
|e verfasserin
|4 aut
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| 773 |
0 |
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|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 197(2018) vom: 08. Dez., Seite 6-18
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnns
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| 773 |
1 |
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|g volume:197
|g year:2018
|g day:08
|g month:12
|g pages:6-18
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| 856 |
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|u http://dx.doi.org/10.1016/j.clim.2018.08.011
|3 Volltext
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