التفاصيل البيبلوغرافية
| العنوان: |
Lipopolysaccharide-dependent transcriptional regulation of PU.1 in microglial cells. |
| المؤلفون: |
Mandal, Chanchal, Yoon, Taeho, Park, Ji Yoon, Jung, Kyoung Hwa, Chai, Young Gyu |
| المصدر: |
Molecular & Cellular Toxicology; Jan2020, Vol. 16 Issue 1, p51-61, 11p |
| مستخلص: |
Backgrounds: PU.1 is a pioneer transcription factor and a master regulator of the myeloid lineage. However, the role of PU.1 in lipopolysaccharide-dependent microglial activation has yet to be investigated. So, this study was conducted to determine the effects of PU.1 in LPS-induced activation of microglial cells. Methods: We knocked out PU.1 in murine BV-2 cells using the CRISPR-Cas9 system to investigate the role of PU.1 in the expression of immune-related genes. We performed RNA sequencing (RNA-seq) of PU.1 KO and BV-2 cells to analyze the gene expression patterns in PU.1 KO cells and compare them to those in wild-type BV-2 cells. The validation of differential expressions was achieved by qRT-PCR. To explore this regulatory role of PU.1, ChIP sequencing for PU.1 and H3K27Ac was performed. The sequencing result was further confirmed by ChIP-qPCR. Results: RNA sequencing and subsequent bioinformatic analysis revealed that the expression of most of the immune-related genes was suppressed in the absence of PU.1. Proinflammatory chemokine genes were differentially expressed in LPS-treated PU.1 KO cells. The ChIP sequencing result followed by ChIP-qPCR revealed a LPS-mediated increase in the enrichment of PU.1 binding in pro-inflammatory chemokine gene promoters and enhancer regions in wild-type BV-2 cells. There was no enrichment of PU.1 in PU.1 KO cells. Conclusion: The above-mentioned results suggest that PU.1 is directly involved in regulating the immune response and that this regulation of inflammatory chemokines is LPS-dependent. We hope that PU.1 would be an option for limiting neurodegeneration in a diverse range of neurological disorders. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
