Project description:We explored the relationship between the evolutionary dynamics of CTCF binding and the functional stability of higher order genome structures, by performing ChIP-seq experiments in closely related Mus species or strains and intersecting with Hi-C-derived topologically associating domains (TADs) and expression data. Experiments were performed in adult male liver samples, using input control sets.
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.
Project description:The large antigen receptor (AgR) loci in T and B lymphocytes have many bound CTCF sites, most of which are only occupied in lymphocytes, while only the CTCF sites at the far end of each locus near enhancers or J genes tend to be bound in non-lymphoid cells also. However, despite the generalized lymphocyte restriction of CTCF binding in AgR loci, the Igκ locus is the only locus which also shows significant lineage-specificity (T vs. B cells) and developmental stage-specificity (pre-B, not pro-B) in CTCF binding. Cohesin is often bound at the same sites as CTCF, and cohesin is thought to create long range chromatin contacts by loop extrusion, with its translocation stopped by convergently oriented CTCF sites. Importantly, cohesin binding shows greater lineage- and stage- specificity than CTCF at most loci, thus providing more specificity to the CTCF/cohesin loops in AgR loci. Since all the CTCF sites within the large V portions of the Igh and TCRβ loci have the same orientation, this suggests either a lack of requirement for convergent CTCF sites creating loops, or indicates an absence of any loops between CTCF sites within the V region portion of those loci but only loops to the convergent sites at the D‐J‐enhancer end of each locus. The V region portions of the Igκ and TCRα δ loci, in contrast, have CTCF sites in both orientations, providing many options for creating CTCF-mediated loops throughout the loci. The immune system may have developed unique utilization of CTCF sites to generate lymphocyte-specific long-range loops to facilitate the formation of diverse antigen receptor repertoires.