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Accessibility of promoter DNA is not the primary determinant of chromatin-mediated gene regulation.
Genome Research ( IF 7 ) Pub Date : 2019-09-11 , DOI: 10.1101/gr.249326.119
Răzvan V Chereji 1 , Peter R Eriksson 1 , Josefina Ocampo 1 , Hemant K Prajapati 1 , David J Clark 1
Affiliation  

DNA accessibility is thought to be of major importance in regulating gene expression. We test this hypothesis using a restriction enzyme as a probe of chromatin structure and as a proxy for transcription factors. We measured the digestion rate and the fraction of accessible DNA at almost all genomic AluI sites in budding yeast and mouse liver nuclei. Hepatocyte DNA is more accessible than yeast DNA, consistent with longer linkers between nucleosomes, suggesting that nucleosome spacing is a major determinant of accessibility. DNA accessibility varies from cell to cell, such that essentially no sites are accessible or inaccessible in every cell. AluI sites in inactive mouse promoters are accessible in some cells, implying that transcription factors could bind without activating the gene. Euchromatin and heterochromatin have very similar accessibilities, suggesting that transcription factors can penetrate heterochromatin. Thus, DNA accessibility is not likely to be the primary determinant of gene regulation.

中文翻译:

启动子DNA的可及性不是染色质介导的基因调控的主要决定因素。

DNA可及性被认为在调节基因表达中具有重要意义。我们使用限制性内切酶作为染色质结构的探针并作为转录因子的替代物来检验这一假设。我们测量了酵母和小鼠肝核中几乎所有基因组AluI位点的消化率和可及DNA的比例。肝细胞DNA比酵母DNA更易接近,这与核小体之间的更长连接子一致,表明核小体间距是可及性的主要决定因素。DNA的可访问性因细胞而异,因此每个细胞中基本上没有位点可访问或不可访问。失活的小鼠启动子中的AluI位点可在某些细胞中访问,这意味着转录因子可以结合而不激活基因。常染色质和异染色质具有非常相似的可及性,表明转录因子可以穿透异染色质。因此,DNA可及性不可能是基因调控的主要决定因素。
更新日期:2019-11-01
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