Role of chromatin structure in regulating gene expression: the hsp26 gene of Drosophila melanogaster.
Role of chromatin structure in regulating gene expression: the hsp26 gene of Drosophila melanogaster.
复制标题
染色质结构在调节基因表达中的作用：果蝇的 hsp26 基因。
DOI：
10.1101/sqb.1993.058.01.012
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Wallrath,LL
中科院分区：
文献类型：
--
作者：
Elgin,SC;Granok,H;Lu,Q;Wallrath,LL
Our goal is to understand the contribution to gene regulation made by the basic structure of the 100 chromatin fiber and the contribution made by the packaging of the 100,~ chromatin fiber into a euchromatic or heterochromatic domain. The pattern of protein/DNA interactions along a given gene within intact nuclei can be mapped by using recombinant DNA probes to assess patterns of DNA modification or cleavage. The use of such techniques has shown that the bulk of the DNA in a eukaryotic nucleus is packaged in a nucleosomal array. However, sites at the 5'ends of active or inducible genes are commonly, observed to be hypersensitive to cleavage by DNase I (Wu 1980; for review, see Elgin 1988; Gross and Garrard 1988). Such DNase-I-hypersensitive sites (DH sites) have been shown both by biochemical analysis and by mapping studies to be nucleosome-free regions, discontinuities in the normal nucleosomal array (see, eg, McGhee et al. 1981; Thomas and Elgin 1988). DH sites have been observed at the 5'ends of active genes with such consistency as to suggest that a nucleosome-free configuration is required for promoter activity. This in turn suggests that nucleosome formation may function to block gene expression, specifically by blocking access to the TATA box or other regulatory elements. This possibility has been supported by in vitro studies showing that a promoter site assembled into a nucleosome structure is not utilized by RNA polymerase II, whereas the presence of a nucleosome downstream from the start site is not a major impediment to transcription (see, eg, Lorch et al. 1987). In vivo experiments have also supported the idea that nucleosomes can serve as general repressors of transcriptional activity. A loss of nucleosome assembly (caused by loss of histone H4 synthesis) in yeast results in basal-level, or in some cases, induced levels, of transcription from a wide array of genes not normally so expressed (Han and Grunstein 1988; Durrin et al. 1992).It is reasonable therefore to suggest that the presence of appropriate DH sites, ie, of specific discontinuities in the nucleosome array, is required for gene expression. Mapping studies of chromatin structure have indicated that this requirement is met in two ways: Either the gene is" preset" in an appropriate chromatin structure, or it undergoes" remodeling" as a critical
