A conserved enhancer regulates Il9 expression in multiple lineages

Byunghee Koh, Amina Abdul Qayum, Rajneesh Srivastava, Yongyao Fu, Benjamin J. Ulrich, Sarath Chandra Janga, Mark Kaplan

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Number of pages1
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Nov 15 2018

Fingerprint

Interleukin-9
genes
deletion
gene expression
immunity
cells
upstream
mice
coding
Transcription Factors
tumors
Genes
activation
Cytokines
Allergies
Gene encoding
Regulator Genes
Gene expression
Tumors
Immunity

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Koh, B., Abdul Qayum, A., Srivastava, R., Fu, Y., Ulrich, B. J., Janga, S. C., & Kaplan, M. (2018). A conserved enhancer regulates Il9 expression in multiple lineages. Nature Communications, 9(1). https://doi.org/10.1038/s41467-018-07202-0

A conserved enhancer regulates Il9 expression in multiple lineages. / Koh, Byunghee; Abdul Qayum, Amina; Srivastava, Rajneesh; Fu, Yongyao; Ulrich, Benjamin J.; Janga, Sarath Chandra; Kaplan, Mark.

In: Nature Communications, Vol. 9, No. 1, 15.11.2018.

Research output: Contribution to journalArticle

Koh, B, Abdul Qayum, A, Srivastava, R, Fu, Y, Ulrich, BJ, Janga, SC & Kaplan, M 2018, 'A conserved enhancer regulates Il9 expression in multiple lineages', Nature Communications, vol. 9, no. 1. https://doi.org/10.1038/s41467-018-07202-0
Koh B, Abdul Qayum A, Srivastava R, Fu Y, Ulrich BJ, Janga SC et al. A conserved enhancer regulates Il9 expression in multiple lineages. Nature Communications. 2018 Nov 15;9(1). https://doi.org/10.1038/s41467-018-07202-0
Koh, Byunghee ; Abdul Qayum, Amina ; Srivastava, Rajneesh ; Fu, Yongyao ; Ulrich, Benjamin J. ; Janga, Sarath Chandra ; Kaplan, Mark. / A conserved enhancer regulates Il9 expression in multiple lineages. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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