Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA101555 | ENA |
REPOSITORIES: ENA
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Project description:PAX5 is a tumor suppressor in B-ALL, while the role of PAX5 fusion proteins in B-ALL development is largely unknown. Here we studied the function of PAX5-ETV6 and PAX5- FOXP1 in mice expressing these proteins from the Pax5 locus. Both proteins arrested Blymphopoiesis at the pro-B-to-pre-B cell transition and, contrary to their proposed dominantnegative role, did not interfere with the expression of most Pax5 target genes. Pax5-Etv6, but not Pax5-Foxp1, cooperated with loss of the Cdkna2a/b tumor suppressor in promoting B-ALL development. Regulated Pax5-Etv6 target genes identified in these B-ALLs encode proteins implicated in pre-BCR signaling and migration/adhesion, which could contribute to the proliferation, survival and tissue infiltration of leukemic B-cells. Together with similar observations made in human PAX5-ETV6+ B-ALLs, these data identified PAX5-ETV6 as a potent oncoprotein. 36 samples in total: A) 24 RNA-Seq samples in 5 cell types: pro-B (5 genotypes, 2-4 replicates) large pre-B (2 genotypes, 2 replicates each) small pre-B (1 genotype, 2 replicates) lymph node (1 genotype, 3 replicates) bone marrow (1 genotype, 2 replicates) B) 12 ChIP-Seq samples in 2 cell types: pro-B (H3K27me3, H3K9ac, H3K4me2, H3K4me3, H3K27ac, 1 replicate each; Pax5Etv6 ChIP, Prd ChIP, 2 replicates each; Pax5 ChIP 1 replicate) lymph node (1 genotype, 2 replicates).
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Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
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