Regulatory effects of theUty/Ddx3ylocus on neighboring chromosome Y genes and autosomal mRNA transcripts in adult mouse non-reproductive cells

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>In addition to sperm-related genes, the male-specific chromosome Y (chrY) contains a class of ubiquitously expressed and evolutionary conserved dosage-sensitive regulator genes that include the neighboring <jats:italic>Uty, Ddx3y</jats:italic> and (in mice) <jats:italic>Eif2s3y</jats:italic> genes. However, no study to date has investigated the functional impact of targeted mutations of any of these genes within adult non-reproductive somatic cells. We thus compared adult male mice carrying a gene trap within their <jats:italic>Uty</jats:italic> gene (<jats:italic>Uty<jats:sup>GT</jats:sup></jats:italic>) to their wild-type (WT) isogenic controls, and performed deep sequencing of RNA and genome-wide profiling of chromatin features in extracts from either cardiac tissue, cardiomyocyte-specific nuclei or purified cardiomyocytes. The apparent impact of <jats:italic>Uty<jats:sup>GT</jats:sup></jats:italic> on gene transcription concentrated mostly on chrY genes surrounding the locus of insertion, <jats:italic>i.e. Uty, Ddx3y</jats:italic>, long non-coding RNAs (lncRNAs) contained within their introns and <jats:italic>Eif2s3y</jats:italic>, in addition to possible effects on the autosomal <jats:italic>Malat1</jats:italic> lncRNA. Notwithstanding, <jats:italic>Uty<jats:sup>GT</jats:sup></jats:italic> also caused coordinate changes in the abundance of hundreds of mRNA transcripts related to coherent cell functions, including RNA processing and translation. The results altogether indicated that tightly co-regulated chrY genes had nonetheless more widespread effects on the autosomal transcriptome in adult somatic cells, most likely due to mechanisms other than just transcriptional regulation of corresponding protein-coding genes.</jats:p>

Sex-specific transcriptomic and epitranscriptomic signatures of PTSD-like fear acquisition

“…These mice did experience a novel environment, and their gene expression profile should therefore be considered not as “baseline” but as mildly stressed. There were 129 differentially expressed genes in the amygdala of females compared with males, including a number of genes previously identified as sexually dimorphic ( Figures S1 A and S1B) ( Yang et al., 2006 ; Deschepper, 2020 ). Importantly, 5.1% of dimorphic expression changes observed within this female versus male control comparison were also observed in response to fear conditioning ( Figures S1 C, Tables S3 , and S4 ).…”