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.

Src promotes castration-recurrent prostate cancer through androgen receptor-dependent canonical and non-canonical transcriptional signatures

“…In the latter case, the overlapping ChIP peaks (found in Intron2 of CDX2 ) flank a non-canonical ARBS motif (Figure 8D), CACTCCAGCCTGGG, similar to the one we identified in LNCaP[Src527F] cells only (Figure 8A; motif #2), as well as an enhancer identified by CAGE analysis [88]. Interestingly, CDX2 is not identified in the ARDGB as a DHT-induced gene in LNCaP cells, nor is it identified in recent TOP2B ChIP-seq analyses [89, 90]. AR binding to this site is potentiated in DHT-treated LNCaP[Src527F] only (Figure 8E), whereas the binding of TOP2B to the same region is potentiated by Src but unaffected by DHT (Figure 8F).…”

TOP2B: The First Thirty Years

“…A number of groups have reported TOP2B ChIP-seq studies, the first reported by Sano et al in 2008, using rat cells [ 153 ]. More recent studies have reported ChIP-seq from human MCF7 cells [ 154 ], primary mouse B cells [ 89 ], mouse liver [ 87 ] and mouse brain [ 155 , 156 ]. Chip-seq analyses in humans [ 154 ] and mouse [ 87 ] identify transcription factor binding sites within the peak sequences associated with topoisomerase IIB; these included CTCF, SP1, EGR1, PAX5, and TFAP2.…”

“…More recent studies have reported ChIP-seq from human MCF7 cells [ 154 ], primary mouse B cells [ 89 ], mouse liver [ 87 ] and mouse brain [ 155 , 156 ]. Chip-seq analyses in humans [ 154 ] and mouse [ 87 ] identify transcription factor binding sites within the peak sequences associated with topoisomerase IIB; these included CTCF, SP1, EGR1, PAX5, and TFAP2. Furthermore, as described above, Uusküla-Reimand et al [ 87 ] also showed that TOP2B is associated with CTCF and members of the cohesin complex at domain boundaries.…”

Genome Organization Drives Chromosome Fragility

“…Recent ChIP-seq analysis indicates that TOP2B binding is not confined to promoters, but is generally associated with open chromatin (Uuskula-Reimand et al, 2016). TOP2B has been shown to physically interact with CTCF and cohesin (Uuskula-Reimand et al, 2016; Witcher and Emerson, 2009), and to be enriched in CTCF/cohesin-bound regions (Madabhushi et al, 2015; Manville et al, 2015; Uuskula-Reimand et al, 2016). Thus, it has been hypothesized that TOP2B may play a role in solving topological constraints associated with chromosome architecture in a tissue- and transcriptional dependent manner (Uuskula-Reimand et al, 2016).…”