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¹ Department of Cell Biology, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064
² Department of Genetics, Case Western Reserve University, Cleveland, OH 44106
³ Laboratory of Receptor Biology and Gene Expression and ⁴ Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
⁵ Department of Biology and ⁶ Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, NC 27599

Correspondence to Miroslav Dundr: mirek.dundr{at}rosalindfranklin.edu; or A. Gregory Matera: agmatera{at}email.unc.edu

Although bulk chromatin is thought to have limited mobility within the interphase eukaryotic nucleus, directed long-distance chromosome movements are not unknown. Cajal bodies (CBs) are nuclear suborganelles that nonrandomly associate with small nuclear RNA (snRNA) and histone gene loci in human cells during interphase. However, the mechanism responsible for this association is uncertain. In this study, we present an experimental system to probe the dynamic interplay of CBs with a U2 snRNA target gene locus during transcriptional activation in living cells. Simultaneous four-dimensional tracking of CBs and U2 genes reveals that target loci are recruited toward relatively stably positioned CBs by long-range chromosomal motion. In the presence of a dominant-negative mutant of β-actin, the repositioning of activated U2 genes is markedly inhibited. This supports a model in which nuclear actin is required for these rapid, long-range chromosomal movements.

M. Dundr and J.K. Ospina contributed equally to this paper.

Abbreviations used in this paper: CB, Cajal body; CMV, cytomegalovirus; dn, dominant negative; Dox, doxycycline; snRNA, small nuclear RNA; Tet, tetracycline; wt, wild type.

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