Molecular Co-occupancy Identifies Transcription Factor Binding Cooperativity In Vivo.
Mol Cell
; 81(2): 255-267.e6, 2021 01 21.
Article
em En
| MEDLINE
| ID: mdl-33290745
ABSTRACT
Gene activation requires the cooperative activity of multiple transcription factors at cis-regulatory elements (CREs). Yet, most transcription factors have short residence time, questioning the requirement of their physical co-occupancy on DNA to achieve cooperativity. Here, we present a DNA footprinting method that detects individual molecular interactions of transcription factors and nucleosomes with DNA in vivo. We apply this strategy to quantify the simultaneous binding of multiple transcription factors on single DNA molecules at mouse CREs. Analysis of the binary occupancy patterns at thousands of motif combinations reveals that high DNA co-occupancy occurs for most types of transcription factors, in the absence of direct physical interaction, at sites of competition with nucleosomes. Perturbation of pairwise interactions demonstrates the function of molecular co-occupancy in binding cooperativity. Our results reveal the interactions regulating CREs at molecular resolution and identify DNA co-occupancy as a widespread cooperativity mechanism used by transcription factors to remodel chromatin.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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DNA
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Nucleossomos
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Pegada de DNA
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Elementos Reguladores de Transcrição
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article