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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Balasubramani, A; Shibata, Y; Crawford, GE; Baldwin, AS; Hatton, RD; Weaver, CT

Published Date

  • July 23, 2010

Published In

Volume / Issue

  • 33 / 1

Start / End Page

  • 35 - 47

PubMed ID

  • 20643337

Pubmed Central ID

  • 20643337

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2010.07.004

Language

  • eng

Conference Location

  • United States