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Nucleic Acids Res ; 48(19): 10867-10876, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33051686

RESUMO

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.


Assuntos
Carcinogênese/genética , Montagem e Desmontagem da Cromatina , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Drosophila , Redes Reguladoras de Genes , Células HCT116 , Humanos , Proteínas Proto-Oncogênicas c-myc/metabolismo , Processos Estocásticos
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