Transcription of carbonyl reductase 1 is regulated by DNA topoisomerase II beta. Issue 20 (30th August 2020)

• Record Type: Journal Article
• Authors: Khazeem, Mushtaq M.; Cowell, Ian G.; Harkin, Lauren F.; Casement, John W.; Austin, Caroline A.
• Is Part Of: FEBS letters. Volume 594:Issue 20(2020)
• Page Start: 3395
• Page End: 3405
• Publication Date: 2020-08-30
• Subjects: carbonyl reductase 1 -- cardiotoxicity -- CBR1 -- DNA topoisomerase -- TOP2B -- topologically associating domains; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13904
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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‐ Cas9 gene editing. We identified carbonyl reductase 1 ( CBR1 ) among the most significantly downregulated genes in these TOP2B‐null cells. Reduced CBR1 expression was accompanied by loss of binding of the transcription factors USF2 and MAX to the CBR1 promoter. We describe possible mechanisms by which loss of TOP2B results in CBR1 downregulation. To our knowledge, this is the first report of a link between TOP2B and CBR1 . Abstract :