Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Balasubramani A 

PROVIDER: S-EPMC2994316 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Balasubramani Anand A   Shibata Yoichiro Y   Crawford Gregory E GE   Baldwin Albert S AS   Hatton Robin D RD   Weaver Casey T CT  

Immunity 20100701 1


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-depende  ...[more]

Similar Datasets

| S-EPMC3273639 | biostudies-literature
| S-EPMC2978326 | biostudies-literature
| S-EPMC2701970 | biostudies-literature
| S-EPMC3602893 | biostudies-literature
| S-EPMC7343331 | biostudies-literature
| S-EPMC4370097 | biostudies-literature
| S-EPMC2869028 | biostudies-literature
| S-EPMC3346311 | biostudies-literature
| S-EPMC2923829 | biostudies-literature
| S-EPMC5954277 | biostudies-literature