Genome-wide mapping of the cohesin complex in the yeast Saccharomyces cerevisiae

Genome-wide mapping of the cohesin complex in the yeast Saccharomyces cerevisiae
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DOI:
10.1371/journal.pbio.0020259
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发表时间:
2004-09-01
期刊:
影响因子:
9.8
通讯作者:
Gerton, JL
Gerton, JL
中科院分区:
生物学1区
文献类型:
--
作者:
Glynn, EF;Megee, PC;Gerton, JL

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在真核细胞中,黏连蛋白将姐妹染色单体维系在一起,直至在有丝分裂过程中它们分离进入子细胞。我们利用染色质免疫沉淀结合微阵列分析(ChIP - chip)对酿酒酵母减数分裂和有丝分裂染色体上黏连蛋白的结合情况进行了全基因组描述。一个名为PeakFinder的计算机程序能够灵活、自动地识别和注释ChIP - chip数据中黏连蛋白结合峰。黏连蛋白位点在减数分裂和有丝分裂中高度保守,这表明在不同的发育过程中染色体具有共同的基础结构。这些位点以11kb的半周期性间隔出现,且与A + T含量相关。位点的数量与染色体大小相关;然而,相邻位点的结合似乎并不协同。我们观察到黏连蛋白位点与收敛转录单元之间的区域存在非常强的相关性。转录和黏连蛋白结合之间的明显不相容性在减数分裂和有丝分裂中均存在。进一步的实验表明,转录延伸进入黏连蛋白结合位点会移除黏连蛋白。黏连蛋白位点与减数分裂重组位点之间呈负相关,这表明减数分裂交换对黏连蛋白所提供的染色体结构敏感。有丝分裂和减数分裂中黏连蛋白结合的全基因组视图为探索其他基因组中的黏连蛋白和黏连作用提供了一个重要框架。
In eukaryotic cells, cohesin holds sister chromatids together until they separate into daughter cells during mitosis. We have used chromatin immunoprecipitation coupled with microarray analysis (Chip chip) to produce a genome-wide description of cohesin binding to meiotic and mitotic chromosomes of Saccharomyces cerevisiae. A computer program, PeakFinder, enables flexible, automated identification and annotation of cohesin binding peaks in Chip chip data. Cohesin sites are highly conserved in meiosis and mitosis, suggesting that chromosomes share a common underlying structure during different developmental programs. These sites occur with a semiperiodic spacing of 11 kb that correlates with AT content. The number of sites correlates with chromosome size; however, binding to neighboring sites does not appear to be cooperative. We observed a very strong correlation between cohesin sites and regions between convergent transcription units. The apparent incompatibility between transcription and cohesin binding exists in both meiosis and mitosis. Further experiments reveal that transcript elongation into a cohesin-binding site removes cohesin. A negative correlation between cohesin sites and meiotic recombination sites suggests meiotic exchange is sensitive to the chromosome structure provided by cohesin. The genome-wide view of mitotic and meiotic cohesin binding provides an important framework for the exploration of cohesins and cohesion in other genomes.