MeCP2 is involved in random mono-allelic expression for a subset of human autosomal genes

Abstract

Widespread random monoallelic gene expression (RMAE) effects influence about 10% of human genes. However, the mechanisms by which RME of autosomal genes is established and those by which it is maintained both remain open questions. Because the choice of allelic expression is randomly performed cell-by-cell, the RMAE mechanism is not observable in non-clonal cell populations or in whole tissues. Several target genes of MeCP2, the gene involved in Rett syndrome (RTT), have been previously described as subject to RMAE, suggesting that MeCP2 may be involved in the establishment and / or maintenance of RME of autosomal genes. To improve our knowledge on this largely unknown phenomenon, and to study the role of MeCP2 in RMAE, we compared RMA gene expression profiles in clonal cell cultures expressing wild-type MeCP2 versus mutant MeCP2 from a RTT patient carrying a pathogenic nonsense variant. Our data clearly demonstrated that MeCP2 deficiency does not affect significantly allelic gene expression of X-linked genes, imprinted genes as well as the RMAE profile in the majority of genes. However, the functional deficiency in MeCP2 appeared to disrupt the mono-allelic or the bi-allelic expression of at least 49 genes allowing us to define a specific signature of MECP2 mutated clones.

Pseudoautosomal gene SHOX exhibits sex-biased random monoallelic expression and contributes to sex difference in height

“…Consequently, the clones were classified into four groups according to the expression patterns of SHOX; (i) biallelic expression (reference allele ratios of between 0.2 and 0.8), (ii) skewed biallelic expression (reference allele ratios of between 0.1 and 0.2 or between 0.8 and 0.9), (iii) MAE (reference allele ratios of ≤ 0.1 or ≥ 0.9), and (iv) null expression (31). For clones with SHOX null expression, we amplified COL1A1 mRNA to confirm the quality of the mRNA sample.…”