本期〈Science〉两篇论文揭示基因调控点是动态的,而不是像过去认为的那样是静态的。在真核细胞中,DNA是包装在染色质中的,染色质是由调控基因的组蛋白组成的信息存贮。Yoshiko Mito和同事研究了果蝇染色质中组蛋白H3的置换率,Michael F. Dion和同事在酵母中作了同样的观察。两个小组分别报告了组蛋白H3置换率随调控点的不同而有高度的不同,在基因组的编码区最“安静”,而在已知的染色质边界元件的蛋白质结合点上表现出极高的置换水平。在这些区域,表观遗传标记必须处于不断变化的状态,才能使它们快速和动态的调制成为可能。
部分英文原文:
Science 9 March 2007:
Vol. 315. no. 5817, pp. 1408 - 1411
DOI: 10.1126/science.1134004
Histone Replacement Marks the Boundaries of cis-Regulatory Domains
Yoshiko Mito,1,2 Jorja G. Henikoff,1 Steven Henikoff1,3*
Cellular memory is maintained at homeotic genes by cis-regulatory elements whose mechanism of action is unknown. We have examined chromatin at Drosophila homeotic gene clusters by measuring, at high resolution, levels of histone replacement and nucleosome occupancy. Homeotic gene clusters display conspicuous peaks of histone replacement at boundaries of cis-regulatory domains superimposed over broad regions of low replacement. Peaks of histone replacement closely correspond to nuclease-hypersensitive sites, binding sites for Polycomb and trithorax group proteins, and sites of nucleosome depletion. Our results suggest the existence of a continuous process that disrupts nucleosomes and maintains accessibility of cis-regulatory elements.
1 Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
2 Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
3 Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
* To whom correspondence should be addressed. E-mail: Oliver.Rando@umassmed.edu
Science 9 March 2007:
Vol. 315. no. 5817, pp. 1405 - 1408
DOI: 10.1126/science.1134053
Dynamics of Replication-Independent Histone Turnover in Budding Yeast
Michael F. Dion,1* Tommy Kaplan,2,3* Minkyu Kim,4 Stephen Buratowski,4 Nir Friedman,2 Oliver J. Rando1
Chromatin plays roles in processes governed by different time scales. To assay the dynamic behavior of chromatin in living cells, we used genomic tiling arrays to measure histone H3 turnover in G1-arrested Saccharomyces cerevisiae at single-nucleosome resolution over 4% of the genome, and at lower (265 base pair) resolution over the entire genome. We find that nucleosomes at promoters are replaced more rapidly than at coding regions and that replacement rates over coding regions correlate with polymerase density. In addition, rapid histone turnover is found at known chromatin boundary elements. These results suggest that rapid histone turnover serves to functionally separate chromatin domains and prevent spread of histone states.
1 Faculty of Arts and Sciences, Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
2 School of Computer Science and Engineering, The Hebrew University, Jerusalem 91904, Israel.
3 Department of Molecular Genetics and Biotechnology, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
4 Department of Biological Chemistry and Molecular Pharmacology, Harvard University, 240 Longwood Avenue, Boston, MA 02115, USA.
* These authors contributed equally to this work.
Present address: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
To whom correspondence should be addressed. E-mail: Oliver.Rando@umassmed.edu