Journal Article

Paternally expressed genes predominate in the placenta

Harman, Rebecca, Clark, Andrew G., Wang, Xu, Miller, Donald C., Antczak, Douglas F.

2013

Overview

The discovery of genomic imprinting through studies of manipulated mouse embryos indicated that the paternal genome has a major influence on placental development. However, previous research has not demonstrated paternal bias in imprinted genes. We applied RNA sequencing to trophoblast tissue from reciprocal hybrids of horse and donkey, where genotypic differences allowed parent-of-origin identification of most expressed genes. Using this approach, we identified a core group of 15 ancient imprinted genes, of which 10 were paternally expressed. An additional 78 candidate imprinted genes identified by RNA sequencing also showed paternal bias. Pyrosequencing was used to confirm the imprinting status of six of the genes, including the insulin receptor (INSR), which may play a role in growth regulation with its reciprocally imprinted ligand, histone acetyltransferase-1 (HAT1), a gene involved in chromatin modification, and lymphocyte antigen 6 complex, locus G6C, a newly identified imprinted gene in the major histocompatibility complex. The 78 candidate imprinted genes displayed parent-of-origin expression bias in placenta but not fetus, and most showed less than 100% silencing of the imprinted allele. Some displayed variability in imprinting status among individuals. This variability results in a unique epigenetic signature for each placenta that contributes to variation in the intrauterine environment and thus presents the opportunity for natural selection to operate on parent-of-origin differential regulation. Taken together, these features highlight the plasticity of imprinting in mammals and the central importance of the placenta as a target tissue for genomic imprinting.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Alleles / Amino acids / Animals / antigens / asses / Base Sequence / Biological Sciences / chromatin / Embryos / Epigenesis, Genetic / Epigenetics / Equidae - embryology / Equidae - genetics / Equidae - metabolism / Female / Fetus / Gene expression / Gene Expression Profiling / Genes / Genomes / Genomic Imprinting / Genomics / Girdles / histones / Horses / Horses - embryology / Horses - genetics / Horses - metabolism / Hybridization, Genetic / Hybrids / insulin receptors / loci / Lymphocytes / major histocompatibility complex / Male / Mammals / Methylation / mice / Mules / natural selection / Placenta / Placenta - embryology / Placenta - metabolism / Plasticity / Polymorphism, Single Nucleotide / Pregnancy / RNA / sequence analysis / Tissues / trophoblast