Abstract
Heterochromatin is a structurally compacted region of chromosomes in which transcription and recombination are inactivated1,2. DNA replication is temporally regulated in heterochromatin, but the molecular mechanism for regulation has not been elucidated. Among heterochromatin loci in Schizosaccharomyces pombe, the pericentromeric region and the silent mating-type (mat) locus replicate in early S phase, whereas the sub-telomeric region does not3,4,5, suggesting complex mechanisms for regulation of replication in heterochromatic regions. Here, we show that Swi6, an S. pombe counterpart of heterochromatin protein 1 (HP1), is required for early replication of the pericentromeric region and the mat locus. Origin-loading of Sld3, which depends on Dfp1/Dbf4-dependent kinase Cdc7 (DDK), is stimulated by Swi6. An HP1-binding motif within Dfp1 is required for interaction with Swi6 in vitro and for early replication of the pericentromeric region and mat locus. Tethering of Dfp1 to the pericentromeric region and mat locus in swi6-deficient cells restores early replication of these loci. Our results show that a heterochromatic protein positively regulates initiation of replication in silenced chromatin by interacting with an essential kinase.
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Acknowledgements
We thank Hiroyuki Araki for critical reading and Yoshinori Watanabe for providing CFP-chromodomain constructs. M.T.H. is a Research Fellow of the Japan Society for the Promotion of Science. This study was supported by a Grant-in-Aid for JSPS Fellows to M.T.H., and in part by a Grant-in-Aid to H.M. and to J.N. from the Ministry of Education, Science, Technology, Sports and Culture, Japan.
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M.T.H. and H.M. designed the project and wrote the paper; M.T.H. performed the experiments; J.N. provided important experimental materials and advice. All authors contributed to the interpretation of the results and edited the manuscript.
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Hayashi, M., Takahashi, T., Nakagawa, T. et al. The heterochromatin protein Swi6/HP1 activates replication origins at the pericentromeric region and silent mating-type locus. Nat Cell Biol 11, 357–362 (2009). https://doi.org/10.1038/ncb1845
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DOI: https://doi.org/10.1038/ncb1845
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