Upregulation of imprinted genes in mice: an insight into the intensity of gene expression and the evolution of genomic imprinting.
Imprinted genes are expressed monoallelically because one of the two copies is silenced epigentically in a parent-of-origin pattern. This pattern of expression is controlled by differential marking of parental alleles by DNA methylation and chromatin modifications, including both suppressive and permissive histone acetylation and methylation. Suppressive histone modifications mark silenced alleles of imprinted genes, while permissive histone modifications mark the active alleles, suggesting the possibility that imprinted genes would show upregulation in gene expression. However, it is currently unknown whether imprinted genes show such upregulation. To address this question in mice, we estimated the intensity of expression of 59 genes relative to the rest of the genome by analyzing microarray data. Expression levels of 24 genes were validated using quantitative real-time PCR (qPCR). Expression of imprinted genes was found to be upreguled in various adult and embryonic mouse tissues. Consistent with their functions in growth and development, imprinted genes were found to be highly expressed in extraembryonic tissues and progressively upregulated during early embryonic development. In conclusion, upregulation of imprinted genes found in this study is similar to the dosage compensation (twofold upregulation) recently reported for X-linked genes. It has been proposed that the twofold upregulation of X-linked genes has been coupled with low transcriptional variation (noise) which could lead to deleterious effects on the organism. Results of this study suggest a general need for imprinted genes in the mouse to be upregulated to certain levels in order to avoid deleterious effects of variation in gene expression.
Zaitoun
Ismail
I
Department of Dairy Science, University of Wisconsin, Madison, WI, USA.
Downs
Karen M
KM
Rosa
Guilherme J M
GJ
Khatib
Hasan
H
D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting / Q000235:genetics*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000235:genetics*