Comparative structure, proximal promoter elements, and chromosome locationof the human eosinophil major basic protein genes

Human eosinophil major basic protein (MBP) is strongly implicated as a medi ator of disease, especially bronchial asthma. We recently isolated a highly divergent human homologue of MBP (MBPH). Given human MBP's importance in d isease and the restricted expression of it and human MBPH, we isolated the 4.6-kb human MBPH gene (HGMW-approved symbol PRG3). Comparisons among the h uman MBP (PRG2), human MBPH, and murine MBP-1 (mMBP-1; Prg2) genes suggest that the human MBP and mMBP-1 genes are more closely related than either is to the human MBPH gene. Proximal promoters of these three genes show conse rvation of potential binding sites far IK2 and STAT and of a known GATA sit e. However, a known C/EBP site is altered in the human MBPH gene's proximal promoter. The human MBP and MBPH genes localized to chromosome 11 in the c entromere to 11q12 region. Thus, the human MBP and MBPH genes have diverged considerably, probably following a gene duplication event. Furthermore, th e identified conserved and distinct proximal promoter elements likely contr ibute to the eosinophil-restricted and relatively reduced transcription of the human MBPH gene. (C) 2001 Academic Press.