Topoisomerase II beta interacts with cohesin and CTCF at topological domain borders.

Topoisomerase II beta interacts with cohesin and CTCF at topological domain borders.
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DOI:
10.1186/s13059-016-1043-8
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发表时间:
2016-08-31
期刊:
影响因子:
12.3
通讯作者:
Wilson MD
Wilson MD
中科院分区:
生物学1区
文献类型:
--
作者:
Uusküla-Reimand L;Hou H;Samavarchi-Tehrani P;Rudan MV;Liang M;Medina-Rivera A;Mohammed H;Schmidt D;Schwalie P;Young EJ;Reimand J;Hadjur S;Gingras AC;Wilson MD

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第二类DNA拓扑异构酶(TOP2)通过在复制和转录过程中产生瞬时双链断裂来调节DNA拓扑结构。拓扑异构酶IIβ(TOP2B)在发育和分化的后期促进基因的快速表达和功能。为了对TOP2B的基因组生物学有新的认识,我们使用蛋白质组学(BioID)、染色质免疫沉淀和高通量染色体构象捕获(Hi-C)来鉴定新的近端TOP2B蛋白相互作用,并在碱基对分辨下表征TOP2B结合的基因组图谱。我们的人类TOP2B近端蛋白相互作用网络包括与rDNA生物学相关的粘附素复合体成员和核仁蛋白。TOP2B与小鼠基因组上的DNase I超敏感位点、等位基因特异性转录因子(Tf)结合以及进化上保守的Tf结合位点相关联。大约一半的CTCF/凝聚力结合区与TOP2B结合一致。TOP2B、CTCF和粘附素位点的碱基对分辨芯片-Exo图谱显示,这些蛋白质在基因组上相对于CTCF基序具有显著的结构有序性。这些有序的TOP2B-CTCF-粘附素位点位于拓扑结合结构域(TADS)的边界两侧,TOP2B位于结构域环的外部,粘附素位于结构域环的内部。TOP2B定位于解决不同顺式调控元件的拓扑问题,它的占据是TADS两侧CTCF/粘附素结合位点高度有序和普遍存在的特征。本文的在线版本(doi:10.1186/s13059-0161043-8)包含补充材料,授权用户可以使用。
Type II DNA topoisomerases (TOP2) regulate DNA topology by generating transient double stranded breaks during replication and transcription. Topoisomerase II beta (TOP2B) facilitates rapid gene expression and functions at the later stages of development and differentiation. To gain new insight into the genome biology of TOP2B, we used proteomics (BioID), chromatin immunoprecipitation, and high-throughput chromosome conformation capture (Hi-C) to identify novel proximal TOP2B protein interactions and characterize the genomic landscape of TOP2B binding at base pair resolution. Our human TOP2B proximal protein interaction network included members of the cohesin complex and nucleolar proteins associated with rDNA biology. TOP2B associates with DNase I hypersensitivity sites, allele-specific transcription factor (TF) binding, and evolutionarily conserved TF binding sites on the mouse genome. Approximately half of all CTCF/cohesion-bound regions coincided with TOP2B binding. Base pair resolution ChIP-exo mapping of TOP2B, CTCF, and cohesin sites revealed a striking structural ordering of these proteins along the genome relative to the CTCF motif. These ordered TOP2B-CTCF-cohesin sites flank the boundaries of topologically associating domains (TADs) with TOP2B positioned externally and cohesin internally to the domain loop. TOP2B is positioned to solve topological problems at diverse cis-regulatory elements and its occupancy is a highly ordered and prevalent feature of CTCF/cohesin binding sites that flank TADs. The online version of this article (doi:10.1186/s13059-016-1043-8) contains supplementary material, which is available to authorized users.
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