Characterization of the sequence and architectural constraints of the regulatory and core regions of the human interleukin-2 promoter.
The cytokine interleukin-2 (IL-2) is produced by T cells when they recognize a foreign antigen. Transcription of the IL-2 gene is tightly controlled by the combined actions of multiple transcriptional activators. However, the contribution of sequences in the IL-2 core promoter and the architecture of the IL-2 regulatory region to setting levels of IL-2 transcription are not understood. We have probed these properties of the human IL-2 promoter to understand how the regulatory and core promoter regions cooperate in response to T cell stimulation, thereby setting high levels of inducible transcription. We found that the IL-2 core promoter contains a TATA box that is critical for inducible expression. Moreover, the spacing and orientation between the IL-2 regulatory and core promoter regions is important for setting the level of transcription. The regulatory region of the IL-2 promoter is capable of mediating high levels of expression even when the helical phasing between transcription factor binding sites is perturbed. Although long considered an enhancer, our studies indicate that the regulatory region in the IL-2 promoter is better considered as a proximal regulatory element, since it lacks multiple properties associated with enhancer elements.
Weaver
Jessica R
JR
Department of Chemistry and Biochemistry, University of Colorado at Boulder, 215 UCB, Boulder, CO 80309-0215, USA.
Good
Kristi
K
Walters
Ryan D
RD
Kugel
Jennifer F
JF
Goodrich
James A
JA
D001483:Base Sequence; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017421:Sequence Analysis; D016385:TATA Box / Q000235:genetics; D014158:Transcription, Genetic
D007376:Interleukin-2