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MYC assembles and stimulates topoisomerases 1 & 2 in a “topisome” [CAD-seq]

ABSTRACT: High-intensity transcription and replication supercoil DNA to levels that can impede or halt these processes. As a potent transcription amplifier and replication accelerator, the proto-oncogene MYC must somehow manage these high levels of torsional stress. By comparing gene expression with the recruitment of topoisomerases and MYC to promoters, we surmised a direct association of MYC with Topoisomerases 1 (TOP1) and 2A (TOP2A) that was confirmed in vitro and in vivo. Beyond recruiting topoisomerases, MYC directly stimulates their activities in vitro and in vivo. We identify a MYC-nucleated “topoisome” complex that unites and increases the levels of both both TOP1 and TOP2, as well as their activities at promoters and enhancers. Whether TOP2A or TOP2B is included in the topoisome, is dictated by the presence of c-MYC or MYCN, respectively. Thus, in vivo and in vitro, MYC assembles tools that simplify DNA topology and promote genome function under high output conditions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE181448 | GEO | 2021/12/09

REPOSITORIES: GEO

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MYC assembles and stimulates topoisomerases 1 & 2 in a “topisome” [ChIP-seq]

Project description:High-intensity transcription and replication supercoil DNA to levels that can impede or halt these processes. As a potent transcription amplifier and replication accelerator, the proto-oncogene MYC must somehow manage these high levels of torsional stress. By comparing gene expression with the recruitment of topoisomerases and MYC to promoters, we surmised a direct association of MYC with Topoisomerases 1 (TOP1) and 2A (TOP2A) that was confirmed in vitro and in vivo. Beyond recruiting topoisomerases, MYC directly stimulates their activities in vitro and in vivo. We identify a MYC-nucleated “topoisome” complex that unites and increases the levels of both both TOP1 and TOP2, as well as their activities at promoters and enhancers. Whether TOP2A or TOP2B is included in the topoisome, is dictated by the presence of c-MYC or MYCN, respectively. Thus, in vivo and in vitro, MYC assembles tools that simplify DNA topology and promote genome function under high output conditions.

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