Inactivation of the H-2Klk gene could involve the substitutions of methylated CpGs.
By the isolation of overlapping cosmid clones and 'chromosome walking' studies from the H-2Kk gene, we have obtained cosmid clones encoding the H-2Klk gene from two separate cosmid libraries. The nucleotide sequence of one of the clones was determined. The cloned H-2Klk gene could be transcribed in vitro to give a normal H-2 class I mRNA of 1.7 kb. However, the deletion of four nucleotides in exon 3 of the H-2Klk gene results in a translation termination codon at the beginning of exon 4. In agreement with this, when expressed in human cells, the H-2Klk gene gave a truncated, cytoplasmic polypeptide of Mr 36,000. Therefore, although the H-2Klk gene is homologous to other class I MHC genes in its molecular organization and nucleotide sequence, it is a pseudogene. When compared to the nucleotide sequence of the H-2Kk gene, the H-2Klk gene has undergone many substitutions of methylated CpG residues (meCpG). This represents further evidence to suggest that this gene is inactive.
Institute of Molecular and Cell Biology, National University of Singapore.
B C
BC
Sim
F G
FG
Grosveld
K M
KM
Hui
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D016386:Chromosome Walking; D003001:Cloning, Molecular; D003360:Cosmids; D005805:Genes, MHC Class I; D008040:Genetic Linkage; D006183:H-2 Antigens / Q000235:genetics*; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation
D006183:H-2 Antigens