Genome-wide ChIP-seq analysis of human TOP2B occupancy in MCF7 breast cancer epithelial cells

Catriona Manville, Kayleigh Smith, Zbyslaw Sondka, Holly Ashlene Rance, Simon Cockell, Ian Cowell, Ka Cheong Lee, Nicholas Morris, Kay Padget, Graham Jackson, Caroline Austin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)
45 Downloads (Pure)

Abstract

We report the whole genome ChIP seq for human TOP2B from MCF7 cells. Using three different peak calling methods, regions of binding were identified in the presence or absence of the nuclear hormone estradiol, as TOP2B has been reported to play a role in ligand-induced transcription. TOP2B peaks were found across the whole genome, 50% of the peaks fell either within a gene or within 5 kb of a transcription start site. TOP2B peaks coincident with gene promoters were less frequently associated with epigenetic features marking active promoters in estradiol treated than in untreated cells. Significantly enriched transcription factor motifs within the DNA sequences underlying the peaks were identified. These included SP1, KLF4, TFAP2A, MYF, REST, CTCF, ESR1 and ESR2. Gene ontology analysis of genes associated with TOP2B peaks found neuronal development terms including axonogenesis and axon guidance were significantly enriched. In the absence of functional TOP2B there are errors in axon guidance in the zebrafish eye. Specific heparin sulphate structures are involved in retinal axon targeting. The glycosaminoglycan biosynthesis-heparin sulphate/heparin pathway is significantly enriched in the TOP2B gene ontology analysis, suggesting changes in this pathway in the absence of TOP2B may cause the axon guidance faults.
Original languageEnglish
Pages (from-to)1436-1447
JournalBiology Open
Volume4
Issue number11
Early online date12 Oct 2015
DOIs
Publication statusPublished - 1 Nov 2015

Keywords

  • ChIP seq
  • TOP2B
  • Topoisomerase II

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