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Comparison of the promoter regions of H-2Kb and H-2Kbm1 class I MHC genes.

ABSTRACT: The 2.0 kb-long nucleotide sequences of the promoter regions of two closely related class I genes of the mouse major histocompatibility complex (H-2Kb and H-2Kbm1) have been determined and compared. The promoter sequence of the H-2Kbm1 gene differs from that of the H-2Kb gene by a single deletion of a 'C' at position -456 in the upstream region of H-2Kbm1 gene. The actual existence of this deletion of a single base in genomic DNA has been verified by genomic DNA hybridization, using oligonucleotide probes specific for H-2Kbm1 or H-2Kb respectively. The effect on the enhancer activity of H-2Kbm1 promoter region of the difference at position -456 has been analyzed by the chloramphenicol acetyltransferase (CAT) assay, using appropriate DdeI fragments (-533 to -408 for H-2Kbm1; -534 to -408 for H-2Kb) cloned downstream of pH-2(367)CAT gene construct. The CAT activity determined by the H-2Kbm1 fragment was about 3-fold higher than that of H-2Kb, a result which probably accounts for the higher level of the H-2Kbm1 transcript and antigen in lymph node cells.

SUBMITTER: Ozawa K

PROVIDER: S-EPMC331177 | biostudies-other | 1990 Jul

REPOSITORIES: biostudies-other

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Comparison of the promoter regions of H-2Kb and H-2Kbm1 class I MHC genes.

Ozawa K K Saka F F Kitabayashi I I Imai T T Soeda E E Israel A A Gachelin G G Yokoyama K K

Nucleic acids research 19900701 14

The 2.0 kb-long nucleotide sequences of the promoter regions of two closely related class I genes of the mouse major histocompatibility complex (H-2Kb and H-2Kbm1) have been determined and compared. The promoter sequence of the H-2Kbm1 gene differs from that of the H-2Kb gene by a single deletion of a 'C' at position -456 in the upstream region of H-2Kbm1 gene. The actual existence of this deletion of a single base in genomic DNA has been verified by genomic DNA hybridization, using oligonucleot ...[more]

PMID: 2377459

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Project description:The vertebrate immune response is mediated through highly adaptive, quickly evolving cell surface receptors, the major histocompatibility complex (MHC). MHC molecules bind and present a diverse array of pathogenic molecules and trigger a cascade of defenses. Use of MHC variation as a marker for population health has also evolved quickly following advances in sequencing methods. We applied a combination of traditional and next generation sequencing methodology to characterize coding (peptide binding region) and regulatory (proximal promoter) sequence variation in MHC Class II DQA and DQB genes between estuarine and coastal populations of the bottlenose dolphin, Tursiops truncatus, an apex predator whose health status is indicative of anthropogenic impacts on the ecosystem. The coding regions had 10 alleles each at DQA and DQB; the promoters had 6 and 7 alleles at DQA and DQB, respectively with variation within key regulatory motifs. Positive selection was observed for the coding regions of both genes while both coding and promoter regions exhibited geographic differences in allele composition that likely indicates diversifying selection across habitats. Most notable was the discovery of a complete duplication of a 14-bp T-box motif in the DQA promoter. Four class II promoter regions (DQA, DQB, DRA, DRB) were characterized in species from four cetacean families (Delphinidae, Monodontidae, Lipotidae, and Physeteridae) and revealed substantial promoter structural diversity across this order. Peptide binding regions may not be the only source of adaptive potential within cetacean MHC for responding to pathogenic threats. These findings are the first analysis of cetacean MHC regulatory motifs, which may divulge unique immunogenetic strategies among cetaceans and reveal how MHC transcriptional control continues to evolve. The combined MHC regulatory and coding data provide new genetic context for distinct vulnerability profiles between coastal and estuarine populations, which are key concerns for health and risk management.

Dataset Information

Comparison of the promoter regions of H-2Kb and H-2Kbm1 class I MHC genes.

Publications

Comparison of the promoter regions of H-2Kb and H-2Kbm1 class I MHC genes.

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