Nuclease-hypersensitive chromatin formed by a CpG island in human DNA cloned as an artificial chromosome in yeast.
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.
Mucha
M
M
Laboratoire de Mutagénèse, Institut J. Monod, Université Paris VI et Paris VII, 2, place Jussieu Tour 43, 75251 Paris, France.
Lisowska
K
K
Goc
A
A
Filipski
J
J
D002843:Chromatin / Q000235:genetics* / Q000648:ultrastructure; D018244:Chromosomes, Artificial, Yeast; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D003850:Deoxyribonuclease I; D015226:Dinucleoside Phosphates; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D006801:Humans; D009707:Nucleosomes / Q000235:genetics / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
D002843:Chromatin; D004247:DNA; D003850:Deoxyribonuclease I; D015226:Dinucleoside Phosphates; D005954:Glucosephosphate Dehydrogenase; D006657:Histones; D009707:Nucleosomes; D014157:Transcription Factors; C015772:CpG dinucleotide