Skip to main content
Journal cover image

Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage.

Publication ,  Journal Article
Mukasa, R; Balasubramani, A; Lee, YK; Whitley, SK; Weaver, BT; Shibata, Y; Crawford, GE; Hatton, RD; Weaver, CT
Published in: Immunity
May 28, 2010

Phenotypic plasticity of T helper 17 (Th17) cells suggests instability of chromatin structure of key genes of this lineage. We identified epigenetic modifications across the clustered Il17a and Il17f and the Ifng loci before and after differential IL-12 or TGF-beta cytokine signaling, which induce divergent fates of Th17 cell precursors. We found that Th17 cell precursors had substantial remodeling of the Ifng locus, but underwent critical additional modifications to enable high expression when stimulated by IL-12. Permissive modifications across the Il17a-Il17f locus were amplified by TGF-beta signaling in Th17 cells, but were rapidly reversed downstream of IL-12-induced silencing of the Rorc gene by the transcription factors STAT4 and T-bet. These findings reveal substantial chromatin instability of key transcription factor and cytokine genes of Th17 cells and support a model of Th17 cell lineage plasticity in which cell-extrinsic factors modulate Th17 cell fates through differential effects on the epigenetic status of Th17 cell lineage factors.

Duke Scholars

Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

May 28, 2010

Volume

32

Issue

5

Start / End Page

616 / 627

Location

United States

Related Subject Headings

  • Transcription Factors
  • T-Lymphocytes, Helper-Inducer
  • T-Lymphocyte Subsets
  • T-Box Domain Proteins
  • Signal Transduction
  • STAT4 Transcription Factor
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Mukasa, R., Balasubramani, A., Lee, Y. K., Whitley, S. K., Weaver, B. T., Shibata, Y., … Weaver, C. T. (2010). Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage. Immunity, 32(5), 616–627. https://doi.org/10.1016/j.immuni.2010.04.016
Mukasa, Ryuta, Anand Balasubramani, Yun Kyung Lee, Sarah K. Whitley, Benjamin T. Weaver, Yoichiro Shibata, Gregory E. Crawford, Robin D. Hatton, and Casey T. Weaver. “Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage.Immunity 32, no. 5 (May 28, 2010): 616–27. https://doi.org/10.1016/j.immuni.2010.04.016.
Mukasa R, Balasubramani A, Lee YK, Whitley SK, Weaver BT, Shibata Y, et al. Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage. Immunity. 2010 May 28;32(5):616–27.
Mukasa, Ryuta, et al. “Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage.Immunity, vol. 32, no. 5, May 2010, pp. 616–27. Pubmed, doi:10.1016/j.immuni.2010.04.016.
Mukasa R, Balasubramani A, Lee YK, Whitley SK, Weaver BT, Shibata Y, Crawford GE, Hatton RD, Weaver CT. Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage. Immunity. 2010 May 28;32(5):616–627.
Journal cover image

Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

May 28, 2010

Volume

32

Issue

5

Start / End Page

616 / 627

Location

United States

Related Subject Headings

  • Transcription Factors
  • T-Lymphocytes, Helper-Inducer
  • T-Lymphocyte Subsets
  • T-Box Domain Proteins
  • Signal Transduction
  • STAT4 Transcription Factor
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice