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Modular utilization of distal cis-regulatory elements controls Ifng gene expression in T cells activated by distinct stimuli.

Publication ,  Journal Article
Balasubramani, A; Shibata, Y; Crawford, GE; Baldwin, AS; Hatton, RD; Weaver, CT
Published in: Immunity
July 23, 2010

Distal cis-regulatory elements play essential roles in the T lineage-specific expression of cytokine genes. We have mapped interactions of three trans-acting factors-NF-kappaB, STAT4, and T-bet-with cis elements in the Ifng locus. We find that RelA is critical for optimal Ifng expression and is differentially recruited to multiple elements contingent upon T cell receptor (TCR) or interleukin-12 (IL-12) plus IL-18 signaling. RelA recruitment to at least four elements is dependent on T-bet-dependent remodeling of the Ifng locus and corecruitment of STAT4. STAT4 and NF-kappaB therefore cooperate at multiple cis elements to enable NF-kappaB-dependent enhancement of Ifng expression. RelA recruitment to distal elements was similar in T helper 1 (Th1) and effector CD8(+) T (Tc1) cells, although T-bet was dispensable in CD8 effectors. These results support a model of Ifng regulation in which distal cis-regulatory elements differentially recruit key transcription factors in a modular fashion to initiate gene transcription induced by distinct activation signals.

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Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

July 23, 2010

Volume

33

Issue

1

Start / End Page

35 / 47

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factor RelA
  • Th1 Cells
  • T-Box Domain Proteins
  • STAT4 Transcription Factor
  • Regulatory Elements, Transcriptional
  • Receptors, Antigen, T-Cell
  • NF-kappa B
  • Mice, Transgenic
  • Mice, Knockout
 

Citation

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Balasubramani, A., Shibata, Y., Crawford, G. E., Baldwin, A. S., Hatton, R. D., & Weaver, C. T. (2010). Modular utilization of distal cis-regulatory elements controls Ifng gene expression in T cells activated by distinct stimuli. Immunity, 33(1), 35–47. https://doi.org/10.1016/j.immuni.2010.07.004
Balasubramani, Anand, Yoichiro Shibata, Gregory E. Crawford, Albert S. Baldwin, Robin D. Hatton, and Casey T. Weaver. “Modular utilization of distal cis-regulatory elements controls Ifng gene expression in T cells activated by distinct stimuli.Immunity 33, no. 1 (July 23, 2010): 35–47. https://doi.org/10.1016/j.immuni.2010.07.004.
Balasubramani A, Shibata Y, Crawford GE, Baldwin AS, Hatton RD, Weaver CT. Modular utilization of distal cis-regulatory elements controls Ifng gene expression in T cells activated by distinct stimuli. Immunity. 2010 Jul 23;33(1):35–47.
Balasubramani, Anand, et al. “Modular utilization of distal cis-regulatory elements controls Ifng gene expression in T cells activated by distinct stimuli.Immunity, vol. 33, no. 1, July 2010, pp. 35–47. Pubmed, doi:10.1016/j.immuni.2010.07.004.
Balasubramani A, Shibata Y, Crawford GE, Baldwin AS, Hatton RD, Weaver CT. Modular utilization of distal cis-regulatory elements controls Ifng gene expression in T cells activated by distinct stimuli. Immunity. 2010 Jul 23;33(1):35–47.
Journal cover image

Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

July 23, 2010

Volume

33

Issue

1

Start / End Page

35 / 47

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factor RelA
  • Th1 Cells
  • T-Box Domain Proteins
  • STAT4 Transcription Factor
  • Regulatory Elements, Transcriptional
  • Receptors, Antigen, T-Cell
  • NF-kappa B
  • Mice, Transgenic
  • Mice, Knockout