Limited evolutionary conservation of imprinting in the human placenta.
The epigenetic phenomenon of genomic imprinting provides an additional level of gene regulation that is confined to a limited number of genes, frequently, but not exclusively, important for embryonic development. The evolution and maintenance of imprinting has been linked to the balance between the allocation of maternal resources to the developing fetus and the mother's well being. Genes that are imprinted in both the embryo and extraembryonic tissues show extensive conservation between a mouse and a human. Here we examine the human orthologues of mouse genes imprinted only in the placenta, assaying allele-specific expression and epigenetic modifications. The genes from the KCNQ1 domain and the isolated human orthologues of the imprinted genes Gatm and Dcn all are expressed biallelically in the human, from first-trimester trophoblast through to term. This lack of imprinting is independent of promoter CpG methylation and correlates with the absence of the allelic histone modifications dimethylation of lysine-9 residue of H3 (H3K9me2) and trimethylation of lysine-27 residue of H3 (H3K27me3). These specific histone modifications are thought to contribute toward regulation of imprinting in the mouse. Genes from the IGF2R domain show polymorphic concordant expression in the placenta, with imprinting demonstrated in only a minority of samples. Together these findings have important implications for understanding the evolution of mammalian genomic imprinting. Because most human pregnancies are singletons, this absence of competition might explain the comparatively relaxed need in the human for placental-specific imprinting.
Monk
D
D
Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, United Kingdom. dmonk@imperial.ac.uk
Arnaud
P
P
Apostolidou
S
S
Hills
F A
FA
Kelsey
G
G
Stanier
P
P
Feil
R
R
Moore
G E
GE
D000483:Alleles; D000579:Amidinotransferases / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D058575:Decorin; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006657:Histones / Q000378:metabolism; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008297:Male; D051379:Mice; D005810:Multigene Family; D010920:Placenta / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011509:Proteoglycans / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000235:genetics
C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006657:Histones; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D011509:Proteoglycans; D017527:Receptor, IGF Type 2; D004247:DNA; D000579:Amidinotransferases; C020681:glycine amidinotransferase