Elf-1 and Stat5 bind to a critical element in a new enhancer of the human interleukin-2 receptor alpha gene.
← Research streamAn 86-nucleotide human IL-2-responsive element (PRRIII) was identified in the 5' noncoding region of the IL-2R alpha gene and conferred IL-2 responsiveness on a heterologous promoter. IL-2 inducibility depended on an overlapping Stat/EBS motif (GASd/EBSd), wi…
Study snapshot
Abstract
The interleukin 2 receptor alpha-chain (IL-2R alpha) gene is a key regulator of lymphocyte proliferation. IL-2R alpha is rapidly and potently induced in T cells in response to mitogenic stimuli. Interleukin 2 (IL-2) stimulates IL-2R alpha. transcription, thereby amplifying expression of its own high-affinity receptor. IL-2R alpha transcription is at least in part controlled by two positive regulatory regions, PRRI and PRRII. PRRI is an inducible proximal enhancer, located between nucleotides -276 and -244, which contains NF-kappaB and SRE/CArG motifs. PRRII is a T-cell-specific enhancer, located between nucleotides -137 and -64, which binds the T-cell-specific Ets protein Elf-1 and HMG-I(Y) proteins. However, none of these proximal regions account for the induction of IL-2R alpha transcription by IL-2. To find new regulatory regions of the IL-2R alpha gene, 8.5 kb of the 5' end noncoding sequence of the IL-2R alpha gene have been sequenced. We identified an 86-nucleotide fragment that is 90% identical to the recently characterized murine IL-2-responsive element (mIL-2rE). This putative human IL-2rE, designated PRRIII, confers IL-2 responsiveness on a heterologous promoter. PRRIII contains a Stat protein binding site that overlaps with an EBS motif (GASd/EBSd). These are essential for IL-2 inducibility of PRRIII/CAT reporter constructs. IL-2 induced the binding of Stat5a and b proteins to the human GASd element. To confirm the physiological relevance of these findings, we carried out in vivo footprinting experiments which showed that stimulation of IL-2R alpha expression correlated with occupancy of the GASd element. Our data demonstrate a major role of the GASd/EBSd element in IL-2R alpha regulation and suggest that the T-cell-specific Elf-1 factor can serve as a transcriptional repressor.
AI evidence extraction
Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.
Main findings
An 86-nucleotide human IL-2-responsive element (PRRIII) was identified in the 5' noncoding region of the IL-2R alpha gene and conferred IL-2 responsiveness on a heterologous promoter. IL-2 inducibility depended on an overlapping Stat/EBS motif (GASd/EBSd), with IL-2 inducing binding of Stat5a and Stat5b to the GASd element; in vivo footprinting showed occupancy of GASd correlated with IL-2R alpha expression stimulation.
Outcomes measured
- IL-2R alpha (interleukin-2 receptor alpha-chain) gene transcription regulation
- Identification/characterization of IL-2-responsive enhancer element (PRRIII)
- Binding of Stat5a/Stat5b and Elf-1 to GASd/EBSd element
- In vivo occupancy (footprinting) of GASd element during IL-2R alpha induction
View raw extracted JSON
{
"study_type": "other",
"exposure": {
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"outcomes": [
"IL-2R alpha (interleukin-2 receptor alpha-chain) gene transcription regulation",
"Identification/characterization of IL-2-responsive enhancer element (PRRIII)",
"Binding of Stat5a/Stat5b and Elf-1 to GASd/EBSd element",
"In vivo occupancy (footprinting) of GASd element during IL-2R alpha induction"
],
"main_findings": "An 86-nucleotide human IL-2-responsive element (PRRIII) was identified in the 5' noncoding region of the IL-2R alpha gene and conferred IL-2 responsiveness on a heterologous promoter. IL-2 inducibility depended on an overlapping Stat/EBS motif (GASd/EBSd), with IL-2 inducing binding of Stat5a and Stat5b to the GASd element; in vivo footprinting showed occupancy of GASd correlated with IL-2R alpha expression stimulation.",
"effect_direction": "unclear",
"limitations": [],
"evidence_strength": "insufficient",
"confidence": 0.78,
"peer_reviewed_likely": "yes",
"keywords": [
"IL-2R alpha",
"interleukin-2 receptor",
"enhancer",
"PRRIII",
"GAS element",
"EBS motif",
"Stat5a",
"Stat5b",
"Elf-1",
"in vivo footprinting",
"transcriptional regulation",
"T cells"
],
"suggested_hubs": []
}AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.
Identifiers and source
DOI: 10.1128/mcb.16.12.6829
PubMed: 8943338