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2016 ; 7
(ä): 10966
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Cajal bodies are linked to genome conformation
#MMPMID26997247
Wang Q
; Sawyer IA
; Sung MH
; Sturgill D
; Shevtsov SP
; Pegoraro G
; Hakim O
; Baek S
; Hager GL
; Dundr M
Nat Commun
2016[Mar]; 7
(ä): 10966
PMID26997247
show ga
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.
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