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基因边界处的负超螺旋调节基因拓扑结构
2020-01-28 22:51

意大利米兰大学Marco Foiani、Yathish Jagadheesh Achar等研究人员合作发现,基因边界处的负超螺旋调节基因拓扑结构。这一研究成果2020年1月22日在线发表于国际学术期刊《自然》。

研究人员报道了酿酒酵母基因在细胞周期的G1和S期的拓扑结构。研究人员在基因边界发现了伤口下的DNA,在编码区域内发现了伤口上的DNA。这一情况不取决于Pol II或S期。Top2和Hmo1在基因边界保留负超螺旋,而Top1在编码区起作用。转录可在编码区域内产生RNA–DNA杂交链,而与复制叉的方向无关。在S期,Hmo1保护来自Top2的伤口DNA,而Top2将Pol II和Top1限制在编码单元,从而抵消了转录泄漏和基因边界处的异常杂交。基因边界处的负超螺旋阻止了超螺旋的扩散以及核小体在编码区的重新定位。DNA环化发生在Top2簇上。研究人员认为,Hmo1以十字形构象锁定基因边界,并与Top2一起调节即使在转录被抑制时仍保留拓扑结构记忆的基因结构。

据了解,转录通过产生拓扑应力和与复制叉的冲突来影响复制染色体的完整性。DNA拓扑异构酶Top1和Top2以及HMGB家族蛋白Hmo1有助于DNA复制和转录。

附:英文原文

Title: Negative supercoil at gene boundaries modulates gene topology

Author: Yathish Jagadheesh Achar, Mohamood Adhil, Ramveer Choudhary, Nick Gilbert, Marco Foiani

Issue&Volume: 2020-01-22

Abstract: Transcription challenges the integrity of replicating chromosomes by generating topological stress and conflicts with forks1,2. The DNA topoisomerases Top1 and Top2 and the HMGB family protein Hmo1 assist DNA replication and transcription3,4,5,6. Here we describe the topological architecture of genes in Saccharomyces cerevisiae during the G1 and S phases of the cell cycle. We found under-wound DNA at gene boundaries and over-wound DNA within coding regions. This arrangement does not depend on Pol II or S phase. Top2 and Hmo1 preserve negative supercoil at gene boundaries, while Top1 acts at coding regions. Transcription generates RNA–DNA hybrids within coding regions, independently of fork orientation. During S phase, Hmo1 protects under-wound DNA from Top2, while Top2 confines Pol II and Top1 at coding units, counteracting transcription leakage and aberrant hybrids at gene boundaries. Negative supercoil at gene boundaries prevents supercoil diffusion and nucleosome repositioning at coding regions. DNA looping occurs at Top2 clusters. We propose that Hmo1 locks gene boundaries in a cruciform conformation and, with Top2, modulates the architecture of genes that retain the memory of the topological arrangements even when transcription is repressed.

DOI: 10.1038/s41586-020-1934-4

Source: https://www.nature.com/articles/s41586-020-1934-4

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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