Project: PRJNA615872
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, 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. Overall design: Frozen left ventricles were obtained from either UtyGt(XS0378)Wtsi (which carries a gene trap within the 4th intron of the Uty gene) or their wild-type counterparts from the isogenic strain C57BL/6.Y<129P2> adult mice. For each strain, the procedure was repeated on three different days in order to obtain triplicate samples for the ATAC-Seq analysis.
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