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| Status |
Public on Jun 26, 2018 |
| Title |
Genome-wide analysis reveals dual roles for Ikaros in regulation of macrophage chromatin state and inflammatory gene expression [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Macrophage activation by bacterial LPS leads to induction of a complex inflammatory gene program dependent on numerous transcription factor families. Here we describe an unexpected role for the lymphoid lineage-determining factor Ikaros in the macrophage LPS response using comprehensive genomic analysis of Ikaros-dependent transcription, DNA binding, and chromatin accessibility. Ikaros exhibited dual repressor and activator roles in LPS-induced gene expression. Consistent with the described function of Ikaros as transcriptional repressor, Ikzf1-/- cells showed enhanced induction for select responses. In contrast, we observed a dramatic defect in expression of delayed response genes and ChIP-seq analyses support a key role for Ikaros in sustained NF-kB chromatin binding. Furthermore, in the absence of Ikaros, a constitutively open chromatin state was coincident with dysregulation of LPS-induced chromatin dynamics, gene expression, and cytokine responses. Our data suggest a central role for Ikaros in coordinating the complex macrophage transcriptional program in response to pathogen challenge.
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| Overall design |
RNA-seq time course (0h, 2h, 4h, 10h) and DNase-seq time course (0h, 3h, 8h) sample replicates from WT and Ikzf KO macrophages; RelA/Ikaros ChIP-seq time course (0h, 3h, 8h) sample replicates and input control DNA samples
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| Contributor(s) |
Oh K, Gottschalk RA, Lounsbury NW, Sun J, Baek S, Wang Z, Dutta B, Hager GL, Sung M, Fraser ID |
| Citation(s) |
29898962 |
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| Submission date |
Jan 13, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Songjoon Baek |
| Organization name |
NCI / NIH
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| Department |
CCR
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| Lab |
LRBGE
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| Street address |
41 Library Drive
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE93602 |
Genome-wide analysis reveals dual roles for Ikaros in regulation of macrophage chromatin state and inflammatory gene expression |
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| Relations |
| BioProject |
PRJNA361269 |
| SRA |
SRP096729 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE93599_RAW.tar |
1.3 Gb |
(http)(custom) |
TAR (of BEDGRAPH, CSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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