A conserved enhancer regulates Il9 expression in multiple lineages
| Autor: | Rajneesh Srivastava, Sarath Chandra Janga, Yongyao Fu, Amina Abdul Qayum, Byunghee Koh, Mark H. Kaplan, Benjamin J. Ulrich |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Science Cellular differentiation medicine.medical_treatment Primary Cell Culture General Physics and Astronomy Biology Article General Biochemistry Genetics and Molecular Biology Conserved sequence Mice 03 medical and health sciences 0302 clinical medicine Gene expression medicine Animals Humans Cell Lineage Enhancer lcsh:Science Transcription factor Gene Conserved Sequence Gene Editing Mice Knockout Regulation of gene expression Binding Sites Multidisciplinary Interleukin-9 Cell Differentiation T-Lymphocytes Helper-Inducer General Chemistry 3. Good health Cell biology Mice Inbred C57BL Enhancer Elements Genetic 030104 developmental biology Cytokine Gene Expression Regulation Female lcsh:Q CRISPR-Cas Systems Protein Binding Transcription Factors 030215 immunology |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-16 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Cytokine genes are regulated by multiple regulatory elements that confer tissue-specific and activation-dependent expression. The cis-regulatory elements of the gene encoding IL-9, a cytokine that promotes allergy, autoimmune inflammation and tumor immunity, have not been defined. Here we identify an enhancer (CNS-25) upstream of the Il9 gene that binds most transcription factors (TFs) that promote Il9 gene expression. Deletion of the enhancer in the mouse germline alters transcription factor binding to the remaining Il9 regulatory elements, and results in diminished IL-9 production in multiple cell types including Th9 cells, and attenuates IL-9-dependent immune responses. Moreover, deletion of the homologous enhancer (CNS-18) in primary human Th9 cultures results in significant decrease of IL-9 production. Thus, Il9 CNS-25/IL9 CNS-18 is a critical and conserved regulatory element for IL-9 production. Interleukin-9 (IL-9) is important for allergy, autoimmunity and tumor immunity, but how its expression is regulated is unclear. Here the authors show the essential function of an enhancer, CNS-25 in mouse and CNS-18 in human, for IL-9 expression, with the deletion of this enhancer severely hampering IL-9 production in mice or human cells. |
| Databáze: | OpenAIRE |
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