Noncanonical genomic imprinting effects in offspring

Paul J. Bonthuis, Wei Chao Huang, Cornelia N. Stacher Hörndli, Elliott Ferris, Tong Cheng, Christopher Gregg

Research output: Contribution to journalArticlepeer-review

Abstract

Here, we describe an RNA-sequencing (RNA-seq)- based approach that accurately detects even modest maternal or paternal allele expression biases at the tissue level, which we call noncanonical genomic imprinting effects. We profile imprinting in the arcuate nucleus (ARN) and dorsal raphe nucleus of the female mouse brain as well as skeletal muscle (mesodermal) and liver (endodermal). Our study uncovers hundreds of noncanonical autosomal and X-linked imprinting effects. Noncanonical imprinting is highly tissue-specific and enriched in the ARN, but rare in the liver. These effects are reproducible across different genetic backgrounds and associated with allele-specific chromatin. Using in situ hybridization for nascent RNAs, we discover that autosomal noncanonical imprinted genes with a tissue-level allele bias exhibit allele-specific expression effects in subpopulations of neurons in the brain in vivo. Wedefine noncanonical imprinted genes that regulate monoamine signaling and determine that these effects influence the impact of inherited mutations on offspring behavior.

Original languageEnglish (US)
Pages (from-to)979-991
Number of pages13
JournalCell Reports
Volume12
Issue number6
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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