title: Genome-wide ChIP-seq analysis of human TOP2B occupancy in MCF7 breast cancer epithelial cells.
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.
authors.affiliation: Institute for Cellular and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Catriona M
authors.initials: CM
authors.lastname: Manville
authors.affiliation: Institute for Cellular and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Kayleigh
authors.initials: K
authors.lastname: Smith
authors.affiliation: Institute for Cellular and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Zbyslaw
authors.initials: Z
authors.lastname: Sondka
authors.affiliation: Institute for Cellular and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Holly
authors.initials: H
authors.lastname: Rance
authors.affiliation: The Bioinformatics Support Unit, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Cockell
authors.affiliation: Institute for Cellular and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Cowell
authors.affiliation: Institute for Cellular and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Ka Cheong
authors.initials: KC
authors.lastname: Lee
authors.affiliation: School of Biomedical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Morris
authors.affiliation: Department of Applied Biology, Northumbria University, Newcastle upon Tyne NE1 8ST, UK.
authors.forename: Kay
authors.initials: K
authors.lastname: Padget
authors.affiliation: Institute for Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Graham H
authors.initials: GH
authors.lastname: Jackson
authors.affiliation: Institute for Cellular and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK caroline.austin@ncl.ac.uk.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Austin
keywords: ChIP seq; TOP2B; Topoisomerase II