github link
Accession IconGSE47437

Lymph node CD4+ T cell and thioglycollate-elicited peritoneal macrophage expression data from nave young and old SJL/J and SJL-ChrY^B10.S male mice

Organism Icon Mus musculus
Sample Icon 24 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Submitter Supplied Information

Description
Understanding the DNA elements that constitute and control the regulatory genome is critical for the appropriate therapeutic management of complex diseases. Here, using chromosome Y (ChrY) consomic mouse strains on the C57BL/6J background, we show that susceptibility to two diverse animal models of autoimmune disease, including experimental allergic encephalomyelitis (EAE) and experimental myocarditis, correlates with the natural variation in copy number of Sly and Rbmy multicopy ChrY genes. In the B6 background, ChrY possesses gene regulatory properties that impact both genome-wide gene expression and the presence of alternative splice variants in pathogenic CD4+ T cells. Using a ChrY consomic strain on the SJL background, we discovered a preference for ChrY-mediated gene regulation in macrophages, the immune cell subset underlying the EAE sexual dimorphism in SJL mice, rather than CD4+ T cells. Importantly, in both genetic backgrounds, an inverse correlation exists between the number of Sly and Rbmy ChrY gene copies and the number of significantly upregulated genes in immune cells, thereby supporting a link between copy number variation of Sly and Rbmy with the ChrY genetic element exerting regulatory properties. Moreover, in humans, an analysis of the CD4+ T cell transcriptome from male multiple sclerosis patients versus healthy controls provides further evidence for an evolutionarily conserved mechanism of gene regulation by ChrY. Thus, these data establish ChrY as a member of the regulatory genome in mammals due to its ability to regulate gene expression and alternative splicing in immune cells linked to disease.
PubMed ID
Total Samples
24
Submitter’s Institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Sex
Age
Specimen part
Processing Information
Additional Metadata
No rows found
Loading...