Transcription of carbonyl reductase 1 is regulated by DNA topoisomerase II beta

被引:3
|
作者
Khazeem, Mushtaq M. [1 ]
Cowell, Ian G. [1 ]
Harkin, Lauren F. [1 ]
Casement, John W. [2 ]
Austin, Caroline A. [1 ]
机构
[1] Newcastle Univ, Fac Med Sci, Biosci Inst, Newcastle Upon Tyne, Tyne & Wear, England
[2] Newcastle Univ, Fac Med Sci, Bioinformat Support Unit, Newcastle Upon Tyne, Tyne & Wear, England
关键词
carbonyl reductase 1; cardiotoxicity; CBR1; DNA topoisomerase; TOP2B; topologically associating domains; GENOME ORGANIZATION; GENE; DOMAINS; CBR1; PROMOTER; ELEMENTS; BREAKS;
D O I
10.1002/1873-3468.13904
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
DNA topoisomerase II beta (TOP2B) has a role in transcriptional regulation. Here, to further investigate transcriptional regulation by TOP2B, we used RNA-sequencing and real-time PCR to analyse the differential gene expression profiles of wild-type and two independent TOP2B-null pre-B Nalm-6 cell lines, one generated by targeted insertion and the other using CRISPR-Cas9gene editing. We identified carbonyl reductase 1 (CBR1) among the most significantly downregulated genes in these TOP2B-null cells. ReducedCBR1expression was accompanied by loss of binding of the transcription factors USF2 and MAX to theCBR1promoter. We describe possible mechanisms by which loss of TOP2B results inCBR1downregulation. To our knowledge, this is the first report of a link between TOP2B andCBR1.
引用
收藏
页码:3395 / 3405
页数:11
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