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

Lookup NU author(s): Catriona Manville, Kayleigh Smith, Dr Zbyslaw Sondka, Holly Rance, Dr Ian Cowell, Ka Lee, Dr Nick Morris, Dr Kay Padget, Professor Graham Jackson, Professor Caroline Austin

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.


Publication metadata

Author(s): Manville CM, Smith K, Sondka Z, Rance H, Cockell S, Cowell IG, Lee KC, Morris NJ, Padget K, Jackson GH, Austin CA

Publication type: Article

Publication status: Published

Journal: Biology Open

Year: 2015

Volume: 4

Issue: 11

Pages: 1436-1447

Online publication date: 12/10/2015

Acceptance date: 10/09/2015

Date deposited: 11/01/2016

ISSN (electronic): 2046-6390

Publisher: Company of Biologists Ltd.

URL: http://dx.doi.org/10.1242/bio.014308

DOI: 10.1242/bio.014308

PubMed id: 26459242


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