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 l ines. HLA-C is hypermethylated in normal adult tissues and 13 cell lin es, while 15 cell lines show the hypomethylated phenotype, Hypomethyla tion of HLA-C strongly correlates with hemizygous deletion of a 9 cM i nterval on 1p35-36.1, suggesting that this region encodes a modifier o f methylation for HLA-C. To test whether hypomethylation of class I HL A genes results from loss of a modifier gene, we fused a hypomethylati ng neuroblastoma cell line with a hypermethylating cell line, Methylat ion of class I HLA genes was induced in the hybrids, Furthermore, meth ylation of HLA-C, -E and -A genes, which are encoded in a 1.4 Mb regio n 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, tha t is deleted in many neuroblastomas.