A Human Modifier of Methylation for Class I HLA Genes (Memo-1) Maps to Chromosomal Bands 1p35–36.1

Abstract

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.