GlobalBiodiversity - between ORC binding and nucleosome...

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between ORC binding and nucleosome turnover, suggesting that turnover facilitates ORC binding. In contrast, other chromatin features that would be expected for open or dynamic chromatin, in- cluding nucleosome density, mononucleosome/ oligonucleosome ratio (a measure of micrococcal nuclease accessibility), H2Av (an H2A.Z his- tone variant enriched in active chromatin), and salt-soluble nucleosomes, show little if any de- pendence on ORC abundance (Fig. 3, H to P). Our findings support the hypothesis that repli- cation origins are determined by chromatin, not by sequence features ( 20 , 21 ). The better quan- titative correspondence of ORC to CATCH-IT data than to other chromatin measurements implies that the ORC occupies DNA that is made acces- sible by nucleosome turnover. In support of this interpretation, we note that very similar corre- spondences are seen when CATCH-IT data are aligned with GAF sites (fig. S9) and that GAF directs nucleosome turnover in vivo ( 22 , 23 ). Our direct strategy for measuring the kinetics of nucleosome turnover does not rely on trans- genes or antibodies but rather uses native his- tones and generic reagents. Thus, CATCH-IT provides a general tool for studying activities that influence nucleosome turnover. With use of CATCH-IT, we found direct evidence that epige- netic maintenance involves nucleosome turnover, a process that erases histone modifications ( 10 ). The fact that EZ is responsible for di- and tri- methylation of H3K27, but the nucleosomes that it modifies turn over faster than a cell cycle, argues against proposals that histone modifica- tions required for cellular memory themselves transmit epigenetic information ( 24 ). Rather, by simply increasing or decreasing accessibility of DNA to sequence-specific binding proteins, regu- lated nucleosome turnover may perpetuate active or silent gene expression states and facilitate ini- tiation of replication. References and Notes 1. S. Henikoff, Nat. Rev. Genet. 9 , 15 (2008). 2. Y. Mito, J. G. Henikoff, S. Henikoff, Nat. Genet. 37 , 1090 (2005). 3. Y. Mito, J. G. Henikoff, S. Henikoff, Science 315 , 1408 (2007). 4. U. Braunschweig, G. J. Hogan, L. Pagie, B. van Steensel, EMBO J. 28 , 3635 (2009). 5. C. M. Chow et al ., EMBO Rep. 6 , 354 (2005). 6. C. Wirbelauer, O. Bell, D. Schübeler, Genes Dev. 19 , 1761 (2005). 7. C. Jin et al ., Nat. Genet. 41 , 941 (2009). 8. S. L. Ooi, J. G. Henikoff, S. Henikoff, Nucleic Acids Res. 38 , e26 (2010). 9. A. Jamai, R. M. Imoberdorf, M. Strubin, Mol. Cell 25 , 345 (2007). 10. M. F. Dion et al ., Science 315 , 1405 (2007). 11. A. Rufiange, P.-E. Jacques, W. Bhat, F. Robert, A. Nourani, Mol. Cell 27 , 393 (2007). 12. Materials and methods are available as supporting material on Science Online. 13. J. A. Prescher, C. R. Bertozzi, Nat. Chem. Biol. 1 ,13 (2005). 14. D. C. Dieterich, A. J. Link, J. Graumann, D. A. Tirrell, E. M. Schuman, Proc. Natl. Acad. Sci. U.S.A. 103 , 9482 (2006). 15. K. Yamasu, T. Senshu, J. Biochem. 107 , 15 (1990). 16. Y. B. Schwartz et al ., Nat. Genet. 38 , 700 (2006). 17. N. Nègre et al ., PLoS Genet. 6 , e1000814 (2010).
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GlobalBiodiversity - between ORC binding and nucleosome...

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