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

Abstract
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.

Citation
Sumida, N., Sifakis, E. G., Kiani, N. A., Ronnegren, A. L., Scholz, B. A., Vestlund, J., … Ohlsson, R. (2020). MYC as a driver of stochastic chromatin networks: implications for the fitness of cancer cells. Nucleic Acids Research. doi:10.1093/nar/gkaa817

Acknowledgements
The authors would like to acknowledge initial assistance from Drs Alejandro Woodbridge and Peter J Svensson as well as support from Science for Life Laboratory, the National Genomics Infrastructure, NGI, and Uppmax for providing assistance in massive parallel sequencing and computational infrastructure as well as the extensive data sets from ENCODE.
Swedish Research Council [VR 2017-04670 and VR 2016-03108]; Swedish Childhood Cancer Fund [PR2017-0132]; Swedish Cancer Society [CAN2017/515, CAN 2016/708]; Lundberg Foundation [2018-0138]; Karolinska Institutet; Novo Nordisk Foundation [NNF16OC0021512]; Cancer Society in Stockholm (2018–2021 and 2019–2021); KA Wallenberg Foundation [KAW 2017.0077]. Funding for open access charge: KA Wallenberg Foundation.

Publisher
Oxford University Press (OUP)

Journal
Nucleic Acids Research

DOI
10.1093/nar/gkaa817

PubMed ID
33051686

Additional Links
https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkaa817/5922798

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