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J Biol Chem, Vol. 275, Issue 2, 1275-1278, January 14, 2000

Nuclease-hypersensitive Chromatin Formed by a CpG Island in Human DNA Cloned as an Artificial Chromosome in Yeast*

Mariusz MuchaDagger §, Katarzyna LisowskaDagger par , Anna Goc§, and Jan FilipskiDagger **

From the Dagger  Laboratoire de Mutagénèse, Institut J. Monod, Université Paris VI et Paris VII, 2, place Jussieu Tour 43, 75251 Paris, France and the § Laboratorium Genetyki, Universytet M. Kopernika, ul. Gagarina 11, 87-100 Torun, Poland

CpG islands are mostly unmethylated GC-, and CpG-rich chromosomal segments overlapping promoter sequences in all housekeeping and many tissue-specific genes in vertebrates. Typically, these islands show an open chromatin structure, low in histone H1 and rich in acetylated histones. We have previously found that the island-like CGCG-rich sites in human DNA are hypersensitive to DNase I upon cloning in Saccharomyces cerevisiae. Here we studied, with a higher resolution, the chromatin formed in yeast by one such site, the CpG island accompanying the human glucose-6-phosphate dehydrogenase gene. We have found two strong hypersensitive sites and several positioned nucleosomes flanking the island despite the absence in yeast of such chromatin fiber-shaping factors as histone H1, methyltransferase, and the tissue-specific transcription factors. This finding, together with similar observations from our laboratories and others supports the idea that variations in GC and/or CpG content substantially contribute to the DNA sequence features modulating the structure of the chromatin. The composition-dependent fluctuations in the accessibility of DNA in the chromatin may constitute an evolutionary advantage and may explain the surprising compositional selection that acts in both the coding and non-coding segments of some genes during mammalian evolution.


* This work was supported by International Association for the Promotion of Cooperation with Scientists from the New Independent States of the former Soviet Union-Ukraine Grant 950092, NATO Grant LST.CLG 974917, and a project of cooperation between France and Poland, POLONIUM 97008.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of the fellowship from the SOCRATES program of cooperation between University Paris 7 and Nicholas Copernicus University of Torun.

par Recipient of the European Molecular Biology short term fellowship. Present address: Instytut Onkologii, Zak<A><AC>l</AC><AC>&cjs1134;</AC></A>ad Biologii Nowotworów. Ul Armii Krajowej 15, 44-100 Gliwice, Poland.

** To whom correspondence should be addressed: Laboratoire de Mutagénèse, Institut J. Monod, 2, place Jussieu Tour 43, 75251 Paris, France. Tel.: 33-1-44276949; Fax: 33-1-44275716; E-mail: filipski@ijm.jussieu.fr.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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