Nuclear domains, called cleavage bodies, are enriched in the RNA 3Ј-processing factors CstF 64 kDa and and CPSF 100 kDa. Cleavage bodies have been found either overlapping with or adjacent to coiled bodies. To determine whether the spatial relationship between cleavage bodies and coiled bodies was influenced by the cell cycle, we performed cell synchronization studies. We found that in G1 phase cleavage bodies and coiled bodies were predominantly coincident, whereas in S phase they were mostly adjacent to each other. In G2 cleavage bodies were often less defined or absent, suggesting that they disassemble at this point in the cell cycle. A small number of genetic loci have been reported to be juxtaposed to coiled bodies, including the genes for U1 and U2 small nuclear RNA as well as the two major histone gene clusters. Here we show that cleavage bodies do not overlap with small nuclear RNA genes but do colocalize with the histone genes next to coiled bodies. These findings demonstrate that the association of cleavage bodies and coiled bodies is both dynamic and tightly regulated and suggest that the interaction between these nuclear neighbors is related to the cell cycle-dependent expression of histone genes.
INTRODUCTIONThe cell nucleus contains various distinct structural and functional domains, each with its own morphology and protein composition Lamond and Earnshaw, 1998). One well-studied nuclear domain is the coiled body, which owes its name to its appearance as a ball of coiled threads in the electron microscope (Monneron and Bernhard, 1969). Coiled bodies are small spherical structures, one to five per nucleus, with a diameter of 0.2-1.0 m. They are evolutionary conserved from plants to mammals, indicating that they have a crucial role in the nucleus (for reviews, see Lamond and Carmo-Fonseca, 1993;Gall et al., 1995). Over the years, many nuclear factors have been found concentrated in coiled bodies. Among these are nucleolar constituents, such as fibrillarin (Raška et al., 1990) and Nopp140 (Meier and Blobel, 1992), U3 small nucleolar RNA (Jiménez-García et al., 1994), and nucleoplasmic factors, such as the general transcription factors TFIIH and TFIIF (Grande et al., 1997;Jordan et al., 1997) and the RNA-processing factors U1, U2, U4/U6, and U7 small nuclear ribonuclear protein (Carmo-Fonseca et al., 1992;Wu and Gall, 1993;Frey and Matera, 1995). The protein p80-coilin is especially enriched inside coiled bodies Raška et al., 1991) and is a hallmark for this nuclear domain. It has become clear that coiled bodies are dynamic structures. Disruption of cellular processes, e.g., by heat shock or drug treatment, rapidly alters the distribution and number of coiled bodies (Carmo-Fonseca et al., 1992). Coiled bodies also undergo changes during the cell cycle. During mitosis they disassemble, and only small remnants are left in the mitotic cell . Coilin enters the nucleus in telophase, but coiled bodies are not formed until later in G1 Ferreira et al., 1994). Thus several lines of investigation indicate that t...