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Effects of a Uty gene trap on the transcriptomic profile of mouse cardiac left ventricles in response to castration

ABSTRACT: Previous results from the laboratory showed that the genetic make up of chromosome Y modulated the effects of castration on the transcriptome of mouse cardiac left ventricles. To test the effect of the chromosome Y Uty locus, the current study tests how castration affects the transcriptomes of cardiac left ventricles from adult male carrying a Uty gene trap (KO) in comparison to wild-type (WT)couterparts.

ORGANISM(S): Mus musculus

PROVIDER: GSE158370 | GEO | 2021/09/19

REPOSITORIES: GEO

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Effects of a Uty gene trap on the transcriptomic profile of mouse cardiac left ventricles in response to castration

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Project description:In addition to sperm-related genes, the male-specific chromosome Y (chrY) contains a class (RNA-Seq) of ubiquitously expressed and evolutionary conserved dosage-sensitive regulator genes, which include the neighboring Uty, Ddx3y and (in mice) Eif2s3y genes. However, the impact of targeted mutations of these genes on the functions of adult non-reproductive somatic cells is still unknown due to lack of experimental evidence. We thus compared adult male mice carrying a gene trap within their Uty gene (UtyGT) to wild-type (WT) isogenic controls, and performed deep sequencing of RNA and genome-wide profiling of chromatin in extracts from either cardiac tissue, cardiomyocyte-specific nuclei and purified cardiomyocytes. The impact of UtyGT on gene transcription was mostly limited to its effects on genes surrounding the locus of insertion, i.e. Uty, Ddx3y, long non-coding RNAs (lncRNAs) contained within their introns, Eif2s3y, as well as on the autosomal Malat1 lncRNA. Notwithstanding, UtyGT also caused coordinate changes in the abundance of hundreds of mRNA transcripts related to particular 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 protein-coding genes.

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