Nurr1 performs its anti-inflammatory function by regulating RasGRP1 expression in neuro-inflammation.

Abstract	Nurr1, a transcription factor belonging to the orphan nuclear receptor, has an essential role in the generation and maintenance of dopaminergic neurons and is important in the pathogenesis of Parkinson' disease (PD). In addition, Nurr1 has a non-neuronal function, and it is especially well known that Nurr1 has an anti-inflammatory function in the Parkinson's disease model. However, the molecular mechanisms of Nurr1 have not been elucidated. In this study, we describe a novel mechanism of Nurr1 function. To provide new insights into the molecular mechanisms of Nurr1 in the inflammatory response, we performed Chromatin immunoprecipitation sequencing (ChIP-Seq) on LPS-induced inflammation in BV2 cells and finally identified the RasGRP1 gene as a novel target of Nurr1. Here, we show that Nurr1 directly binds to the RasGRP1 intron to regulate its expression. Moreover, we also identified that RasGRP1 regulates the Ras-Raf-MEK-ERK signaling cascade in LPS-induced inflammation signaling. Finally, we conclude that RasGRP1 is a novel regulator of Nurr1's mediated inflammation signaling.
Authors	Mihee Oh, Sun Young Kim, Jung-Eun Gil, Jeong-Su Byun, Dong-Wook Cha, Bonsu Ku, Woonghee Lee, Won-Kon Kim, Kyoung-Jin Oh, Eun-Woo Lee, Kwang-Hee Bae, Sang Chul Lee, Baek-Soo Han
Journal	Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 10755 (07 01 2020) ISSN: 2045-2322 [Electronic] England
PMID	32612143 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Chromatin DNA-Binding Proteins Guanine Nucleotide Exchange Factors Lipopolysaccharides NR4A2 protein, human Nr4a2 protein, mouse Nuclear Receptor Subfamily 4, Group A, Member 2 RASGRP1 protein, human Rasgrp1 protein, mouse Transcription Factors
Topics	Animals Cell Line Chromatin (chemistry) DNA-Binding Proteins (metabolism) Dopaminergic Neurons (metabolism) Guanine Nucleotide Exchange Factors (metabolism) HEK293 Cells Humans Inflammation (metabolism) Introns Lipopolysaccharides (chemistry) Mice Microglia (metabolism) Nuclear Receptor Subfamily 4, Group A, Member 2 (metabolism) Parkinson Disease (metabolism) Signal Transduction Transcription Factors (metabolism)

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