Project description:The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. We examined the non-random positioning of Cajal bodies (CBs), major NBs involved in spliceosomal snRNP assembly, and their role in genome organization. CBs are predominantly located at the periphery of chromosome territories at a multi-chromosome interface. Genome-wide chromatin conformation capture analysis (4C-seq) using CB-interacting loci revealed that CB-associated regions are enriched with highly expressed histone genes and U small nuclear and nucleoar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. We observed a number of CB-dependent gene positioning events on chromosome 1. RNAi-mediated disassembly of CBs disrupts the CB-targeting gene clusters and suppresses the expression of U sn/snoRNA and histone genes. This loss of spliceosomal snRNP production resulted in increased splicing noise, even in CB-distal regions. We conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
Project description:The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. We examined the non-random positioning of Cajal bodies (CBs), major NBs involved in spliceosomal snRNP assembly, and their role in genome organization. CBs are predominantly located at the periphery of chromosome territories at a multi-chromosome interface. Genome-wide chromatin conformation capture analysis (4C-seq) using CB-interacting loci revealed that CB-associated regions are enriched with highly expressed histone genes and U small nuclear and nucleoar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. We observed a number of CB-dependent gene positioning events on chromosome 1. RNAi-mediated disassembly of CBs disrupts the CB-targeting gene clusters and suppresses the expression of U sn/snoRNA and histone genes. This loss of spliceosomal snRNP production resulted in increased splicing noise, even in CB-distal regions. We conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.
Project description:The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. We examined the non-random positioning of Cajal bodies (CBs), major NBs involved in spliceosomal snRNP assembly, and their role in genome organization. CBs are predominantly located at the periphery of chromosome territories at a multi-chromosome interface. Genome-wide chromatin conformation capture analysis (4C-seq) using CB-interacting loci revealed that CB-associated regions are enriched with highly expressed histone genes and U small nuclear and nucleoar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. We observed a number of CB-dependent gene positioning events on chromosome 1. RNAi-mediated disassembly of CBs disrupts the CB-targeting gene clusters and suppresses the expression of U sn/snoRNA and histone genes. This loss of spliceosomal snRNP production resulted in increased splicing noise, even in CB-distal regions. We conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.