Project description:The association of host histones with parvoviral DNA is poorly understood. We analyzed the chromatinization and histone acetylation of canine parvovirus DNA during infection by confocal imaging and in situ proximity ligation assay combined with chromatin immunoprecipitation and high-throughput sequencing. We found that at late infection parvovirus replication bodies were rich in histones bearing modifications characteristic of transcriptionally active chromatin, i.e. histone H3 lysine acetylation (H3K27ac). The H3K27ac, in particular, was located in close proximity to the viral DNA-binding protein NS1. Importantly, our results show for the first time that in the chromatinized parvoviral genome, particularly the two viral promoters were rich in H3K27ac. Histone acetyltransferase (HAT) inhibitorefficiently interfered with expression of viral proteins and infection progress. Altogether, our data suggest that acetylation of histones on parvoviral DNA is essential for viral gene expression and completion of viral life cycle.
Project description:The association of host histones with parvoviral DNA is poorly understood. We analyzed the chromatinization and histone acetylation of canine parvovirus DNA during infection by confocal imaging and in situ proximity ligation assay combined with chromatin immunoprecipitation and high-throughput sequencing. We found that at late infection parvovirus replication bodies were rich in histones bearing modifications characteristic of transcriptionally active chromatin, i.e. histone H3 lysine acetylation (H3K27ac). The H3K27ac, in particular, was located in close proximity to the viral DNA-binding protein NS1. Importantly, our results show for the first time that in the chromatinized parvoviral genome, particularly the two viral promoters were rich in H3K27ac. Histone acetyltransferase (HAT) inhibitorefficiently interfered with expression of viral proteins and infection progress. Altogether, our data suggest that acetylation of histones on parvoviral DNA is essential for viral gene expression and completion of viral life cycle. Examination of H3K27 acetylation in CPV infected and non-infected NLFK (Norden laboratory feline kidney) cells. Please note that the result in this study, considering the sequencing, is the fact that the viral genome is chromatinized. Processed data in this case would be the aligned read percentages in control cells (of which 0% aligns to parvoviral genome) and infected cells (of which ~9% only aligns to parvoviral genome and not to the cat genome), which is basically the output of the read aligner software without further processing steps (no peaks or regions were identified for the associated publication). Therefore no processed data was provided, and an exception to GEO processed data requirement was made.
Project description:This SuperSeries is composed of the following subset Series: GSE16087: Gene expression profiles of canine osteosarcoma GSE16088: Gene expression profiles of human osteosarcoma GSE16091: Gene expression profiles of human osteosarcoma, set2 Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy. Two datasets consisting of canine osteosarcoma tumors, canine osteosarcoma cell lines, and three normal tissues and an analogous human dataset were used to define the similarity between human and canine osteosarcoma. A third dataset, human osteosarcoma with outcome data, was then used to suggest that some of the differences between the canine and human osteosarcoma were, perhaps, related to survival.
Project description:Polymorphic transposable elements found in regulatory sequences can impact the associated transactional modules. We investigated such molecular alterations for these elements in the dog genome that evolved from directional selection during domestication. We find that the polymorphic element in canine GTF2I intron 17 is associated with altered looping, and hence distinct cis-regulatory landscapes. We report supporting evidence of an E2F1-DNA binding peak concordant with the altered loop and higher expression of GTF2I exon 18. Additionally, we find altered looping with the canine LIMK1 gene and an increase in LAT2 expression within the loop. At a more global level, we discover differences in pathways regulating the extra-cellular matrix between samples of differential TE number. Our study emphasizes the role of chromatin architecture in social evolution.
Project description:Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy. Profiles of human osteosarcoma, single channel design
Project description:Transcriptional profiling of dog muscle tissue comparing control dogs. tested, genomewide, for genes differentially expressed in muscle between the escapers and the affected dogs. Using Agilent mRNA SurePrint Canine arrays, we compared muscle gene expression of the two escapers, four affected, and four normal dogs at age 2 years.
Project description:Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy. Profiles of dog osteosarcoma and several normal tissues, single channel design, tumor versus normal