Comparative structure, proximal promoter elements, and chromosome location of the human eosinophil major basic protein genes.
Human eosinophil major basic protein (MBP) is strongly implicated as a mediator of disease, especially bronchial asthma. We recently isolated a highly divergent human homologue of MBP (MBPH). Given human MBP's importance in disease 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 human 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 conservation of potential binding sites for IK2 and STAT and of a known GATA site. 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 centromere to 11q12 region. Thus, the human MBP and MBPH genes have diverged considerably, probably following a gene duplication event. Furthermore, the identified conserved and distinct proximal promoter elements likely contribute to the eosinophil-restricted and relatively reduced transcription of the human MBPH gene.
Plager
D A
DA
Department of Immunology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. plager.douglas@mayo.edu
Weiler
D A
DA
Loegering
D A
DA
Johnson
W B
WB
Haley
L
L
Eddy
R L
RL
Shows
T B
TB
Gleich
G J
GJ
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001798:Blood Proteins / Q000096:biosynthesis / Q000235:genetics*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002503:Centromere / Q000648:ultrastructure; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000378:metabolism; D047091:Eosinophil Granule Proteins; D047093:Eosinophil Major Basic Protein; D019143:Evolution, Molecular; D005091:Exons; D015723:Gene Library; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012260:Ribonucleases; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D001798:Blood Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D018076:DNA, Complementary; D047091:Eosinophil Granule Proteins; C479219:Prg3 protein, mouse; D012260:Ribonucleases; D047093:Eosinophil Major Basic Protein