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

    43 Citations (Scopus)
    54 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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