Search

Summary: Noncanonical genomic imprinting can cause biased expression of one parental allele in a tissue; however, the functional relevance of such biases is unclear. To investigate ethological roles for noncanonical imprinting in dopa decarboxylase (Ddc) and tyrosine hydroxylase (Th), we use machine learning to decompose naturalistic foraging in maternal and paternal allele mutant heterozygous mice. We uncover distinct roles for the maternal versus paternal alleles on foraging, where maternal alleles affect sons while daughters are under paternal allelic control. Each parental allele controls specific action sequences reflecting decisions in naive or familiar contexts. The maternal Ddc allele is preferentially expressed in subsets of hypothalamic GABAergic neurons, while the paternal allele predominates in subsets of adrenal cells. Each Ddc allele affects distinct molecular and endocrine components of the brain-adrenal axis. Thus, monoaminergic noncanonical imprinting has ethological roles in foraging and endocrine functions and operates by affecting discrete subsets of cells.

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. We define noncanonical imprinted genes that regulate monoamine signaling and determine that these effects influence the impact of inherited mutations on offspring behavior.