Structural constraints within a trimeric transcriptional regulatory region. Constitutive and interferon-gamma-inducible expression of the HLA-DRA gene.

Constitutive and inducible transcription of the major histocompatibility class II HLA-DRA gene involves the upstream S element and the conserved X and Y elements. In this report we have addressed the roles of spatial constraints and stereospecific alignment between the upstream S and X elements, and the X and Y elements, in both constitutive and interferon-gamma (gamma-IFN)-induced expression. Analysis of the constitutive expression in B cell lines (B-LCL) has previously shown that the X and Y elements must be stereoaligned. Further study reveals that any spacing changes between S and X, regardless of the helical alignment of these two elements, is not tolerated. These same restraints are involved in an inducible system, because the response to gamma-IFN treatment requires both stereo alignment between the X and Y elements and precise spacing between the S and X elements. Neither constitutive nor inducible expression can be restored by correcting the distance and spacing between only the S and Y elements with misalignment of X. These results reveal a common pathway for constitutive and inducible expression that may require either direct or indirect protein complex formation among proteins bound to three highly conserved regulatory elements. We have also evaluated the role of the A/T-rich sequence located immediately 5' of the Y element and show that it exerts little effect on constitutive and gamma-IFN induced DRA expression.