TOP2B是SH-SY5Y细胞经维甲酸处理后发生区室强度变化的必要条件。

IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Erica M Hildebrand, Ian G Cowell, Mushtaq M Khazeem, Snehal Sambare, Ozgun Uyan, Job Dekker, Caroline A Austin
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引用次数: 0

摘要

DNA拓扑异构酶II β (TOP2B)是正确执行某些发育转录程序和信号诱导转录激活所必需的,包括核激素配体(如视黄酸)的转录激活。此外,TOP2B在CCCTC-Binding factor (CTCF)和cohesin (RAD21)占据的基因组位置富集。提示在染色体环和/或建立或维持染色体三维结构方面的作用。这使我们研究了TOP2B失活对反映基因组三维结构的染色体内和染色体间相互作用模式的影响。利用维甲酸反应性SH-SY5Y神经母细胞瘤细胞系模型,我们之前已经证明了维甲酸治疗和TOP2B缺失后许多基因表达的变化。我们在这里报道,这些表达变化在TOP2B null细胞与WT细胞中伴随着令人惊讶的局部染色体组织的微妙变化。然而,我们确实观察到染色体组织在百万碱基规模上的定量变化。首先,缺乏TOP2B确实影响ATRA治疗后发生的室室强度变化。其次,我们观察到超长距离的相互作用,使人联想到有丝分裂细胞中的相互作用,这表明在没有TOP2B的情况下,一些有丝分裂相互作用可能被保留。第三,我们看到着丝粒-端粒相互作用的定量变化,再次表明在大碱基和染色体水平上的全局变化。这些数据支持了一个令人惊讶的结论,即TOP2B在染色体动力学和组织中只起很小的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TOP2B is required for compartment strength changes upon retinoic acid treatment in SH-SY5Y cells.

DNA topoisomerase II beta (TOP2B) is required for correct execution of certain developmental transcriptional programs and for signal-induced transcriptional activation, including transcriptional activation by nuclear hormone ligands such as retinoic acid. In addition, TOP2B is enriched at genomic locations occupied by CCCTC-Binding factor (CTCF) and cohesin (RAD21). suggesting a role in chromosome looping and/or establishing or maintaining aspects of chromosome 3D structure. This led us to investigate the effect of TOP2B inactivation on patterns of intra- and inter- chromosomal interaction that reflect the 3D architecture of the genome. Using the retinoic acid responsive SH-SY5Y neuroblastoma cell line model, we had previously demonstrated many gene expression changes upon retinoic acid treatment and upon deletion of TOP2B. We report here that these expression changes in TOP2B null versus WT cells are accompanied by surprisingly subtle changes in local chromosome organization. However, we do observe quantitative changes in chromosome organization on a megabase scale. First, lack of TOP2B did affect compartment strength changes that occur upon ATRA treatment. Second, we observe an excess of very long-range interactions, reminiscent of interactions seen in mitotic cells, suggesting the possibility that in the absence of TOP2B some mitotic interactions are retained. Third, we see quantitative changes in centromere-telomere interactions, again indicating global changes at the megabase and chromosome level. These data support the surprising conclusion that TOP2B has only a minor role in chromosome dynamics and organization.

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来源期刊
Chromosome Research
Chromosome Research 生物-生化与分子生物学
CiteScore
4.70
自引率
3.80%
发文量
31
审稿时长
1 months
期刊介绍: Chromosome Research publishes manuscripts from work based on all organisms and encourages submissions in the following areas including, but not limited, to: · Chromosomes and their linkage to diseases; · Chromosome organization within the nucleus; · Chromatin biology (transcription, non-coding RNA, etc); · Chromosome structure, function and mechanics; · Chromosome and DNA repair; · Epigenetic chromosomal functions (centromeres, telomeres, replication, imprinting, dosage compensation, sex determination, chromosome remodeling); · Architectural/epigenomic organization of the genome; · Functional annotation of the genome; · Functional and comparative genomics in plants and animals; · Karyology studies that help resolve difficult taxonomic problems or that provide clues to fundamental mechanisms of genome and karyotype evolution in plants and animals; · Mitosis and Meiosis; · Cancer cytogenomics.
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