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IL-1R signaling promotes STAT3 and NF-κB factor recruitment to distal cis-regulatory elements that regulate Il17a/f transcription.

Publication ,  Journal Article
Whitley, SK; Balasubramani, A; Zindl, CL; Sen, R; Shibata, Y; Crawford, GE; Weathington, NM; Hatton, RD; Weaver, CT
Published in: J Biol Chem
October 12, 2018

Interleukin (IL)-1β plays a critical role in IL-6β- and transforming growth factor β (TGFβ)-initiated Th17 differentiation and induction of Th17-mediated autoimmunity. However, the means by which IL-1 regulates various aspects of Th17 development remain poorly understood. We recently reported that IL-1β enhances STAT3 phosphorylation via NF-κB-mediated repression of SOCS3 to facilitate Il17 transcription and Th17 differentiation, identifying an effect of IL-1 signaling on proximal events of STAT3 signaling. Here, we show that IL-1β promotes STAT3 binding to key cis-elements that control IL-17 expression. Additionally, we demonstrate that the IL-1-induced NF-κB factor RelA directly regulates the Il17a/f loci in cooperation with STAT3. Our findings reveal that IL-1 impacts both proximal signaling events and downstream interactions between transcription factors and cis-regulatory elements to promote Il17a/f transcription and Th17 differentiation.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

October 12, 2018

Volume

293

Issue

41

Start / End Page

15790 / 15800

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factor RelA
  • Th17 Cells
  • Signal Transduction
  • STAT3 Transcription Factor
  • Regulatory Sequences, Nucleic Acid
  • Receptors, Interleukin-1 Type II
  • Mice, Inbred C57BL
  • Interleukin-17
  • DNA
 

Citation

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Whitley, S. K., Balasubramani, A., Zindl, C. L., Sen, R., Shibata, Y., Crawford, G. E., … Weaver, C. T. (2018). IL-1R signaling promotes STAT3 and NF-κB factor recruitment to distal cis-regulatory elements that regulate Il17a/f transcription. J Biol Chem, 293(41), 15790–15800. https://doi.org/10.1074/jbc.RA118.002721
Whitley, Sarah K., Anand Balasubramani, Carlene L. Zindl, Ranjan Sen, Yoichiro Shibata, Gregory E. Crawford, Nathaniel M. Weathington, Robin D. Hatton, and Casey T. Weaver. “IL-1R signaling promotes STAT3 and NF-κB factor recruitment to distal cis-regulatory elements that regulate Il17a/f transcription.J Biol Chem 293, no. 41 (October 12, 2018): 15790–800. https://doi.org/10.1074/jbc.RA118.002721.
Whitley SK, Balasubramani A, Zindl CL, Sen R, Shibata Y, Crawford GE, et al. IL-1R signaling promotes STAT3 and NF-κB factor recruitment to distal cis-regulatory elements that regulate Il17a/f transcription. J Biol Chem. 2018 Oct 12;293(41):15790–800.
Whitley, Sarah K., et al. “IL-1R signaling promotes STAT3 and NF-κB factor recruitment to distal cis-regulatory elements that regulate Il17a/f transcription.J Biol Chem, vol. 293, no. 41, Oct. 2018, pp. 15790–800. Pubmed, doi:10.1074/jbc.RA118.002721.
Whitley SK, Balasubramani A, Zindl CL, Sen R, Shibata Y, Crawford GE, Weathington NM, Hatton RD, Weaver CT. IL-1R signaling promotes STAT3 and NF-κB factor recruitment to distal cis-regulatory elements that regulate Il17a/f transcription. J Biol Chem. 2018 Oct 12;293(41):15790–15800.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

October 12, 2018

Volume

293

Issue

41

Start / End Page

15790 / 15800

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factor RelA
  • Th17 Cells
  • Signal Transduction
  • STAT3 Transcription Factor
  • Regulatory Sequences, Nucleic Acid
  • Receptors, Interleukin-1 Type II
  • Mice, Inbred C57BL
  • Interleukin-17
  • DNA