Physical and functional interaction among Irf8 enhancers during dendritic cell differentiation
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ABSTRACT:
PROVIDER: PRJNA1001813 | ENA |
REPOSITORIES: ENA
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Project description:To test if there is a physical interaction between the IRF8 promoter and the rs2280381-containing region, we conducted circular chromatin conformation capture assay in the U937 cell. For the IRF8 viewpoint group, we used CSP6I as the first digested enzyme and NlaIII as the second enzyme. For the rs2280381-containing region, we used MboI as the first digested enzyme and NlaIII as the second enzyme. We use 4C-PCR primer to construct IRF8 point view and rs2280381-containing region 4C library.
2021-07-01 | E-MTAB-10120 | biostudies-arrayexpress
Project description:Type 1 classical dendritic cells (cDC1s) development requires the transcription factor IRF8, and IRF8 mutations cause severe combined immunodeficiency, including disseminated bacille Calmette-Guérin (BCG) disease. IRF8 regulated enhancers are required for Irf8 expression in early DC progenitors and mature cDC1s. The E-protein-dependent +41 kb enhancer gains accessibility and activates transcription in common DC progenitors (CDPs), and its depletion abrogated pre-cDC1s specification. The Batf3-dependent +32 kb enhancer gains accessibility and activates transcription in pre-cDC1 progenitors, and its depletion impaired cDC1 maturation. The +32 kb Irf8 enhancer locus bears an enhancer transcript, and the production of enhancer RNA (eRNA) Gm39266 is dependent on +41 kb Irf8 enhancer. It was unclear whether the +32 kb and +41 kb enhancers act independently or cooperate to regulate Irf8 expression. We dissected the mechanisms using +32/+41 compound heterozygous mice, and found that while the +41 kb enhancer suffices for pre-cDC1 progenitor specification, the +32 kb and +41 kb enhancers must reside on one allele to support cDC1 maturation. The +41 kb enhancer cis-regulates chromatin accessibility and BATF3 binding at +32 kb enhancer, independent of eRNA Gm39266 transcripts or transcription across +32 kb Irf8 enhancer.
2023-03-15 | GSE218991 | GEO
Project description:Type 1 classical dendritic cells (cDC1s) development requires the transcription factor IRF8, and IRF8 mutations cause severe combined immunodeficiency, including disseminated bacille Calmette-Guérin (BCG) disease. IRF8 regulated enhancers are required for Irf8 expression in early DC progenitors and mature cDC1s. The E-protein-dependent +41 kb enhancer gains accessibility and activates transcription in common DC progenitors (CDPs), and its depletion abrogated pre-cDC1s specification. The Batf3-dependent +32 kb enhancer gains accessibility and activates transcription in pre-cDC1 progenitors, and its depletion impaired cDC1 maturation. The +32 kb Irf8 enhancer locus bears an enhancer transcript, and the production of enhancer RNA (eRNA) Gm39266 is dependent on +41 kb Irf8 enhancer. It was unclear whether the +32 kb and +41 kb enhancers act independently or cooperate to regulate Irf8 expression. We dissected the mechanisms using +32/+41 compound heterozygous mice, and found that while the +41 kb enhancer suffices for pre-cDC1 progenitor specification, the +32 kb and +41 kb enhancers must reside on one allele to support cDC1 maturation. The +41 kb enhancer cis-regulates chromatin accessibility and BATF3 binding at +32 kb enhancer, independent of eRNA Gm39266 transcripts or transcription across +32 kb Irf8 enhancer.
2023-03-15 | GSE218990 | GEO
Project description:To understand the mechanism underlying monocyte and dendritic cell development through the regulation of Irf8 expression by the 56 kb downstream (+56 kb) Irf8 enhancer, we performed epigenetic profiling of bone marrow cells and splenocytes from wild-type, the Irf8 +56 kb enhancer-deficient, and IRF8-deficient mice. Taken together with the transcriptome analysis of mononuclear phagocyte lineage cells in these mice, the Irf8 +56 kb enhancer-mediated high Irf8 expression in hematopoietic progenitor cells promote type 1 classical dendritic cell (cDC1) differentiation, while low Irf8 expression in progenitors led to Ly6C+ monocyte development. In addition, IRF8 ChIP-seq of mature cDC1s and monocytes suggested that IRF8 regulates enhancers in cooperation with different transcription factors in each lineage in its expression level.
2020-12-20 | GSE149757 | GEO
Project description:To investigate the role of IRF8 in the inflammatory microenvironment of abdominal aortic aneurysm tissue, bone marrow cells were isolated from the tibias and femurs of 8-week-old male mice and cultured with granulocyte-macrophage colony-stimulating factor and Flt3L cytokines to generate CD103-positive dendritic cells. Cells were harvested on days 9 and 15-16 and stimulated with tumor necrosis factor-alpha. Gene ontology analysis revealed upregulation of T cell activation and chemotaxis in bone marrow-derived dendritic cells from IRF8 overexpression mice, indicating IRF8's role in dendritic cell-T cell interactions. Protein-protein interaction analysis highlighted Cd40 and Fcgr1 as key surface markers. IRF8-related genes were enriched in type I interferon signaling pathways, implicating IRF8 in antigen presentation functions of dendritic cells.
2024-10-10 | GSE278890 | GEO
Project description:To test if lncRNA AC092723.1 play a role in physical interaction between the IRF8 promoter and the rs2280381-containing region, we conducted circular chromatin conformation capture assay in the human primary monocyte. We knock down lncRNA AC092723.1 by electro-transfecting ASOs, the control group is transfected negtive ASOs with no impact on lncRNA AC092723.1.We used CSP6I as the first digested enzyme and NlaIII as the second enzyme. After constructing 4C library,we then utilize 4C-PCR primer to construct IRF8 point view 4C library.
2022-02-25 | E-MTAB-11175 | biostudies-arrayexpress
Project description:Physical and functional interaction between Irf8 enhancers during dendritic cell differentiation
| PRJDB16329 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-04-24 | GSE239952 | GEO
Project description:Autoactivation of lineage-determining transcription factors (TFs) mediates bistable expression to generate distinct cell phenotypes essential for complex body plans. Classical dendritic cells type 1 (cDC1) and type 2 (cDC2) provide non-redundant functions required for defense against distinct immune challenges. Interferon Regulatory Factor 8 (IRF8), the cDC1 lineage-determining TF, undergoes autoactivation in cDC1 progenitors to establish cDC1 identity, yet its expression is downregulated during cDC2 differentiation by an unknown mechanism. This study reveals that the Irf8 +32 kb enhancer, responsible for IRF8 autoactivation, has been tuned to possess low-affinity IRF8 binding sites. Incorporation of multiple high-affinity IRF8 binding sites into the Irf8 +32 kb enhancer induces erroneous IRF8 autoactivation in specified cDC2 progenitors, causing their redirection towards cDC1 and a novel hybrid DC subset with mixed lineage phenotypes. These developmental alterations critically impair both cDC1- and cDC2-dependent arms of immunity. Collectively, our findings underscore the significance of enhancer suboptimization in the developmental segregation of classical dendritic cells required for normal immune function.
2024-08-18 | GSE270060 | GEO
Project description:Cis-regulation between Irf8 enhancers during cDC1 development
| PRJNA906523 | ENA