HIGH-MOBILITY GROUP PROTEIN I(Y) IS REQUIRED FOR FUNCTION AND FOR C-REL BINDING TO CD28 RESPONSE ELEMENTS WITHIN THE GM-CSF AND IL-2 PROMOTERS

CD28 response elements (CD28REs) within cytokine promoters are variant NF-kappa B-binding sites and are essential for transcription in respo nse to CD28 receptor activation in T cells. We show that the CK-1 elem ent (CD28RE) within the GM-CSF promoter binds the RelA and c-Rel trans cription factors in response to CD28 activation. We further show that the high mobility group protein HMG I(Y) can bind to the CD28REs of bo th GM-CSF and IL-2 and that this binding is critical for c-Rel, but no t RelA, binding. A second NF-kappa B site in the GM-CSF promoter that binds p50 and RelA, but neither c-Rel nor HMG I(Y), failed to respond to CD28 activation. Expression of HMG I or c-Rel antisense RNA inhibit ed CD28 activation of the IL-2 and GM-CSF promoters, implying that HMG I(Y) enhancement of c-Rel binding plays an important role in the acti vity of the CD28REs.