title: Cajal bodies are linked to genome conformation.
abstract: The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. Here 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 chromosome 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 or nucleolar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. In particular, 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 results in increased splicing noise, even in CB-distal regions. Therefore, we conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.
authors.affiliation: Department of Cell Biology, Rosalind Franklin University of Medicine and Science, Chicago Medical School, North Chicago, 60064 Ilinois, USA.|Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892 Maryland, USA.
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Rosalind Franklin University of Medicine and Science, Chicago Medical School, North Chicago, 60064 Ilinois, USA.|Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892 Maryland, USA.
authors.forename: Iain A
authors.initials: IA
authors.lastname: Sawyer
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892 Maryland, USA.
authors.forename: Myong-Hee
authors.initials: MH
authors.lastname: Sung
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892 Maryland, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sturgill
authors.affiliation: Department of Cell Biology, Rosalind Franklin University of Medicine and Science, Chicago Medical School, North Chicago, 60064 Ilinois, USA.
authors.forename: Sergey P
authors.initials: SP
authors.lastname: Shevtsov
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892 Maryland, USA.|High-Throughput Imaging Facility (HiTIF), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892 Maryland, USA.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Pegoraro
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892 Maryland, USA.
authors.forename: Ofir
authors.initials: O
authors.lastname: Hakim
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892 Maryland, USA.
authors.forename: Songjoon
authors.initials: S
authors.lastname: Baek
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892 Maryland, USA.
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Hager
authors.affiliation: Department of Cell Biology, Rosalind Franklin University of Medicine and Science, Chicago Medical School, North Chicago, 60064 Ilinois, USA.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Dundr
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics; D020541:Coiled Bodies / Q000235:genetics*; D044127:Epigenesis, Genetic; D056426:Genetic Loci; D015894:Genome, Human; D006367:HeLa Cells; D006657:Histones / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009690:Nucleic Acid Conformation; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics; D012342:RNA, Small Nuclear / Q000235:genetics; D020537:RNA, Small Nucleolar / Q000235:genetics; D015203:Reproducibility of Results; D017384:Sequence Deletion; D017381:Spliceosomes / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D012342:RNA, Small Nuclear; D020537:RNA, Small Nucleolar; D012319:RNA Polymerase II