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| Status |
Public on Dec 31, 2020 |
| Title |
Genomic and epigenomic adaptation in SP-R210 (Myo18A) isoform-deficient macrophages [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Macrophages play fundamental roles in regulation of inflammatory responses to pathogens, resolution of inflammation and tissue repair, and maintenance of tissue homeostasis. The long (L) and short (S) isoforms of SP-R210/MYO18A, a macrophage receptor for surfactant protein A (SP-A) and C1q, regulate basal and inflammatory macrophage phenotype at multiple gene expression, translational, and subcellular levels in addition to their SP-A and C1q-mediated functions; disruption of L renders macrophages hyper-inflammatory, although the underlying mechanism had previously been unexplored. We questioned whether disruption of the L isoform would alter the global genomic responses. RNA sequencing analysis of SP-R210L(DN) macrophages revealed basal and influenza induced upregulation of genes associated with inflammatory pathways, including TLR, RIG-I, NOD, and cytoplasmic DNA signaling, whereas knockdown of both SP-R210 isoforms (L and S) only resulted in increased RIG-I and NOD signaling. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis showed increased genome-wide deposition of the pioneer transcription factor PU.1 in SP-R210L(DN) compared to WT cells. ChIP-seq analysis of histone H3 methylation showed alterations in both repressive (H3K9me3 and H3K27me3) and transcriptionally active (H3K9me3) histone marks. Influenza A virus (IAV) infection, which stimulates an array of cytosolic and TLR-mediated antiviral mechanisms, resulted in differential redistribution between proximal promoter and distal sites and decoupling of PU.1 binding from Toll-like receptor regulated gene promoters in SP-R210L(DN) cells. Our findings suggest that SP-R210L-deficient macrophages are poised with an open PU.1-primed chromatin conformation to rapidly respond to inflammatory and metabolic stimuli.
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| Overall design |
Total 17 samples were analyzed; 5 replicates each for uninfected WT and SP-R210L(DN) cells, 3 replicates for uninfected SP-R210(KO) cells, and 2 replicate each for IAV infected WT and SP-R210L(DN) cells
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| Contributor(s) |
Yau E, Chen Y, Song C, Webb J, Carillo M, Kawasawa YI, Tang Z, Takahashi Y, Umstead TM, Dovat S, Chroneos ZC |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Dec 30, 2020 |
| Last update date |
Jan 02, 2021 |
| Contact name |
Zissis Chroneos |
| E-mail(s) |
zchroneos@pennstatehealth.psu.edu
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| Organization name |
Penn State College of Medicine
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| Department |
Pediatrics
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| Street address |
500 University Drive
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| City |
Hershey |
| State/province |
PA |
| ZIP/Postal code |
17036 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE164036 |
Genomic and epigenomic adaptation in SP-R210 (Myo18A) isoform-deficient macrophages |
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| Relations |
| BioProject |
PRJNA688693 |
| SRA |
SRP299791 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE164034_RAW.tar |
4.9 Mb |
(http)(custom) |
TAR (of BED, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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