Journal Article

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

N. C. Cheng, A. J. K. Chan, M. M. Beitsma, F. Speleman, A. Westerveld and R. Versteeg

in Human Molecular Genetics

Volume 5, issue 3, pages 309-317
Published in print March 1996 | ISSN: 0964-6906
e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/5.3.309
A Human Modifier of Methylation for Class I HLA Genes (Memo-1) Maps to Chromosomal Bands 1p35–36.1

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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.

Journal Article.  5843 words.  Illustrated.

Subjects: Genetics and Genomics

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