Project description:Gene-level analysis of gene expression in immortalized mouse keratinocyte lines that express or lack integrin alpha3beta1 The laminin-332-binding integrin alpha3beta1 is expressed highly in the epidermis, but its roles in regulating gene expression programs that promote normal or pathological skin remodeling have not been underexplored previously. In order to identify genes that are regulated by alpha3beta1 in keratinocytes, we used microarray approaches to identify alpha3beta1-dependent genes in mouse keratinocytes that were immortalized with SV40 large T antigen (i.e., MK cells).
Project description:Gene-level analysis of gene expression in immortalized mouse keratinocyte lines that express integrins alpha3beta1 and alpha9beta1 in different combinations. The integrins alpha3beta1 and alpha9beta1 are expressed highly in the epidermis, but their roles in regulating gene expression programs that promote normal or pathological wound healing have not been explored previously. In order to identify genes that are regulated by these integrins in keratinocytes, we used microarray approaches to identify integrin-dependent genes in mouse keratinocytes that were immortalized with SV40 large T antigen (i.e., MK cells).
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.
Project description:Nucleolus-associated DNA was isolated from MEF cells before and after conditional knock-out of UBF and hybridized against genomic DNA in biological replicates. Two different types of immortalized MEF cells were used. MEFs were immortalized by genetic depletion of p53, iMEFs were immortalized by transfection of the SV40 Tt antigen.
