A human modifier of methylation for class I HLA genes (MEMO-1) maps to chromosomal bands 1p35-36.1.
Class I HLA genes are expressed in almost all tissues, but expression is low or undetectable in many neuroblastomas. We analysed class I HLA methylation in normal tissues and in 28 neuroectodermal tumour cell lines. HLA-C is hypermethylated in normal adult tissues and 13 cell lines, while 15 cell lines show the hypomethylated phenotype. Hypomethylation of HLA-C strongly correlates with hemizygous deletion of a 9 cM interval on 1p35-36.1, suggesting that this region encodes a modifier of methylation for HLA-C. To test whether hypomethylation of class I HLA genes results from loss of a modifier gene, we fused a hypomethylating neuroblastoma cell line with a hypermethylating cell line. Methylation of class I HLA genes was induced in the hybrids. Furthermore, methylation of HLA-C, -E and -A genes, which are encoded in a 1.4 Mb region on 6p21, is correlated in most cell lines. Our results suggest that 1p35-36.1 encodes a modifier of methylation for class I HLA genes, that is deleted in many neuroblastomas.
Cheng
N C
NC
Department of Human Genetics, University of Amsterdam.
Chan
A J
AJ
Beitsma
M M
MM
Speleman
F
F
Westerveld
A
A
Versteeg
R
R
D000483:Alleles; D002459:Cell Fusion / Q000235:genetics; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D005805:Genes, MHC Class I / Q000502:physiology*; D006801:Humans; D008745:Methylation; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured