Chromosome-wide profiling of X-chromosome inactivation and epigenetic states in fetal brain and placenta of the opossum, Monodelphis domestica

Xu Wang, Kory C. Douglas, John L. VandeBerg, Andrew G. Clark, Paul B. Samollow

    Research output: Contribution to journalArticle

    28 Scopus citations

    Abstract

    Evidence from a few genes in diverse species suggests that X-chromosome inactivation (XCI) in marsupials is characterized by exclusive, but leaky inactivation of the paternally derived X chromosome. To study the phenomenon of marsupial XCI more comprehensively, we profiled parent-of-origin allele-specific expression, DNA methylation, and histone modifications in fetal brain and extra-embryonic membranes in the gray, short-tailed opossum (Monodelphis domestica). The majority of X-linked genes (152 of 176 genes with trackable SNP variants) exhibited paternally imprinted expression, with nearly 100% of transcripts derived from the maternal allele; whereas 24 loci (14%) escaped inactivation, showing varying levels of biallelic expression. In addition to recently reported evidence of marsupial XCI regulation by the noncoding Rsx transcript, strong depletion of H3K27me3 at escaper gene loci in the present study suggests that histone state modifications also correlate strongly with opossum XCI. In contrast to mouse, the opossum did not show an association between X-linked gene expression and promoter DNA methylation, with one notable exception. Unlike all other X-linked genes examined, Rsx was differentially methylated on the maternal and paternal X chromosomes, and expression was exclusively from the inactive (paternal) X chromosome. Our study provides the first comprehensive catalog of parent-of-origin expression status for X-linked genes in a marsupial and sheds light on the regulation and evolution of imprinted XCI in mammals.

    Original languageEnglish (US)
    Pages (from-to)70-83
    Number of pages14
    JournalGenome Research
    Volume24
    Issue number1
    DOIs
    StatePublished - Jan 2014

    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

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