Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313385108> ?p ?o ?g. }
Showing items 1 to 70 of
70
with 100 items per page.
- W4313385108 endingPage "67.3" @default.
- W4313385108 startingPage "67.3" @default.
- W4313385108 abstract "Abstract Toll-like receptor (TLR) pathways have been intensively investigated for almost two decades. However, since most studies have focused on the initial signal transduction and transcription events, the mechanisms of late-sustained gene expression are poorly understood. To address this issue, we conducted an RNAi screen for regulators of TLR-induced IL-6 secretion in RAW264.7 macrophages, and identified a novel putative regulator of this process (Hit4). Hit4 was specifically required to sustain the late expression of genes including Il6, Il1a, Nos2 and Lcn2, but did not affect induction of transiently expressed genes such as Nfkbiz, Egr1, and Egr2. This effect of Hit4 was confirmed by CRISPR/Cas9 gene editing and by RNAi knockdown in primary macrophages. Most interestingly, Hit4 functioned specifically in sustaining rather than initiating transcription, as Hit4 depletion showed no effect on the early mRNA transcription before 2 hr for all gene classes. Further mechanistic investigation revealed that Hit4 functioned at the transcriptional level rather than post-transcriptional level, as Hit4 enhanced the level of nascent transcripts at later time points. Moreover, Hit4 KO RAW264.7 macrophages failed to sustain the response to persistent LPS stimulation, showing a response similar to that observed for transient LPS stimulation. This suggests a role for Hit4 in discriminating brief spurious pulses of infectious signal from a more sustained real infection signal. In summary, we have identified a novel transcriptional regulator that functions to sustain transcription of late inflammatory genes, providing important new insight to the control of TLR-induced gene program.(Supported by the Intramural Research Program of NIAID, NIH)" @default.
- W4313385108 created "2023-01-06" @default.
- W4313385108 creator A5028245662 @default.
- W4313385108 creator A5040892667 @default.
- W4313385108 creator A5041569902 @default.
- W4313385108 creator A5056916013 @default.
- W4313385108 date "2017-05-01" @default.
- W4313385108 modified "2023-09-27" @default.
- W4313385108 title "Discovery of a novel transcriptional regulator of sustained TLR-mediated inflammatory responses" @default.
- W4313385108 doi "https://doi.org/10.4049/jimmunol.198.supp.67.3" @default.
- W4313385108 hasPublicationYear "2017" @default.
- W4313385108 type Work @default.
- W4313385108 citedByCount "0" @default.
- W4313385108 crossrefType "journal-article" @default.
- W4313385108 hasAuthorship W4313385108A5028245662 @default.
- W4313385108 hasAuthorship W4313385108A5040892667 @default.
- W4313385108 hasAuthorship W4313385108A5041569902 @default.
- W4313385108 hasAuthorship W4313385108A5056916013 @default.
- W4313385108 hasConcept C104317684 @default.
- W4313385108 hasConcept C138885662 @default.
- W4313385108 hasConcept C150194340 @default.
- W4313385108 hasConcept C165864922 @default.
- W4313385108 hasConcept C166703698 @default.
- W4313385108 hasConcept C173396325 @default.
- W4313385108 hasConcept C179926584 @default.
- W4313385108 hasConcept C27153228 @default.
- W4313385108 hasConcept C41895202 @default.
- W4313385108 hasConcept C54355233 @default.
- W4313385108 hasConcept C62478195 @default.
- W4313385108 hasConcept C67705224 @default.
- W4313385108 hasConcept C6929976 @default.
- W4313385108 hasConcept C86339819 @default.
- W4313385108 hasConcept C86803240 @default.
- W4313385108 hasConcept C95444343 @default.
- W4313385108 hasConceptScore W4313385108C104317684 @default.
- W4313385108 hasConceptScore W4313385108C138885662 @default.
- W4313385108 hasConceptScore W4313385108C150194340 @default.
- W4313385108 hasConceptScore W4313385108C165864922 @default.
- W4313385108 hasConceptScore W4313385108C166703698 @default.
- W4313385108 hasConceptScore W4313385108C173396325 @default.
- W4313385108 hasConceptScore W4313385108C179926584 @default.
- W4313385108 hasConceptScore W4313385108C27153228 @default.
- W4313385108 hasConceptScore W4313385108C41895202 @default.
- W4313385108 hasConceptScore W4313385108C54355233 @default.
- W4313385108 hasConceptScore W4313385108C62478195 @default.
- W4313385108 hasConceptScore W4313385108C67705224 @default.
- W4313385108 hasConceptScore W4313385108C6929976 @default.
- W4313385108 hasConceptScore W4313385108C86339819 @default.
- W4313385108 hasConceptScore W4313385108C86803240 @default.
- W4313385108 hasConceptScore W4313385108C95444343 @default.
- W4313385108 hasIssue "1_Supplement" @default.
- W4313385108 hasLocation W43133851081 @default.
- W4313385108 hasOpenAccess W4313385108 @default.
- W4313385108 hasPrimaryLocation W43133851081 @default.
- W4313385108 hasRelatedWork W1570826421 @default.
- W4313385108 hasRelatedWork W1930517486 @default.
- W4313385108 hasRelatedWork W1990072661 @default.
- W4313385108 hasRelatedWork W2062378380 @default.
- W4313385108 hasRelatedWork W2149228700 @default.
- W4313385108 hasRelatedWork W2172226517 @default.
- W4313385108 hasRelatedWork W2461780163 @default.
- W4313385108 hasRelatedWork W2508597590 @default.
- W4313385108 hasRelatedWork W4281611476 @default.
- W4313385108 hasRelatedWork W4320913447 @default.
- W4313385108 hasVolume "198" @default.
- W4313385108 isParatext "false" @default.
- W4313385108 isRetracted "false" @default.
- W4313385108 workType "article" @default.