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MYC as a driver of stochastic chromatin networks: implications for the fitness of cancer cells.


ABSTRACT: The relationship between stochastic transcriptional bursts and dynamic 3D chromatin states is not well understood. Using an innovated, ultra-sensitive technique, we address here enigmatic features underlying the communications between MYC and its enhancers in relation to the transcriptional process. MYC thus interacts with its flanking enhancers in a mutually exclusive manner documenting that enhancer hubs impinging on MYC detected in large cell populations likely do not exist in single cells. Dynamic encounters with pathologically activated enhancers responsive to a range of environmental cues, involved <10% of active MYC alleles at any given time in colon cancer cells. Being the most central node of the chromatin network, MYC itself likely drives its communications with flanking enhancers, rather than vice versa. We submit that these features underlie an acquired ability of MYC to become dynamically activated in response to a diverse range of environmental cues encountered by the cell during the neoplastic process.

SUBMITTER: Sumida N 

PROVIDER: S-EPMC7641766 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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MYC as a driver of stochastic chromatin networks: implications for the fitness of cancer cells.

Sumida Noriyuki N   Sifakis Emmanouil G EG   Kiani Narsis A NA   Ronnegren Anna Lewandowska AL   Scholz Barbara A BA   Vestlund Johanna J   Gomez-Cabrero David D   Tegner Jesper J   Göndör Anita A   Ohlsson Rolf R  

Nucleic acids research 20201101 19


The relationship between stochastic transcriptional bursts and dynamic 3D chromatin states is not well understood. Using an innovated, ultra-sensitive technique, we address here enigmatic features underlying the communications between MYC and its enhancers in relation to the transcriptional process. MYC thus interacts with its flanking enhancers in a mutually exclusive manner documenting that enhancer hubs impinging on MYC detected in large cell populations likely do not exist in single cells. D  ...[more]

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