Maternal bias and escape from X chromosome imprinting in the midgestation mouse placenta

Dev Biol. 2014 Jun 1;390(1):80-92. doi: 10.1016/j.ydbio.2014.02.020. Epub 2014 Mar 2.

Abstract

To investigate the epigenetic landscape at the interface between mother and fetus, we provide a comprehensive analysis of parent-of-origin bias in the mouse placenta. Using F1 interspecies hybrids between mus musculus (C57BL/6J) and mus musculus castaneus, we sequenced RNA from 23 individual midgestation placentas, five late stage placentas, and two yolk sac samples and then used SNPs to determine whether transcripts were preferentially generated from the maternal or paternal allele. In the placenta, we find 103 genes that show significant and reproducible parent-of-origin bias, of which 78 are novel candidates. Most (96%) show a strong maternal bias which we demonstrate, via multiple mathematical models, pyrosequencing, and FISH, is not due to maternal decidual contamination. Analysis of the X chromosome also reveals paternal expression of Xist and several genes that escape inactivation, most significantly Alas2, Fhl1, and Slc38a5. Finally, sequencing individual placentas allowed us to reveal notable expression similarity between littermates. In all, we observe a striking preference for maternal transcription in the midgestation mouse placenta and a dynamic imprinting landscape in extraembryonic tissues, reflecting the complex nature of epigenetic pathways in the placenta.

Keywords: Imprinting; Parent-of-origin bias; Placenta; RNA sequencing; X-inactivation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 5-Aminolevulinate Synthetase / genetics
  • Amino Acid Transport Systems, Neutral / genetics
  • Animals
  • Chromosomes, Mammalian / genetics*
  • Cluster Analysis
  • Female
  • Gene Expression Regulation, Developmental
  • Genomic Imprinting*
  • Gestational Age
  • Hybridization, Genetic
  • Inheritance Patterns
  • Intracellular Signaling Peptides and Proteins / genetics
  • LIM Domain Proteins / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Proteins / genetics
  • Placenta / embryology
  • Placenta / metabolism*
  • Placentation
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • RNA, Long Noncoding / genetics
  • Sequence Analysis, RNA / methods
  • Species Specificity
  • Transcriptome
  • X Chromosome / genetics*
  • X Chromosome Inactivation

Substances

  • Amino Acid Transport Systems, Neutral
  • Fhl1 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • Muscle Proteins
  • RNA, Long Noncoding
  • SNAT5 protein, mouse
  • XIST non-coding RNA
  • 5-Aminolevulinate Synthetase
  • ALAS2 protein, mouse