Single-molecule regulatory architectures captured by chromatin fiber sequencing.
Science
; 368(6498): 1449-1454, 2020 06 26.
Article
em En
| MEDLINE
| ID: mdl-32587015
ABSTRACT
Gene regulation is chiefly determined at the level of individual linear chromatin molecules, yet our current understanding of cis-regulatory architectures derives from fragmented sampling of large numbers of disparate molecules. We developed an approach for precisely stenciling the structure of individual chromatin fibers onto their composite DNA templates using nonspecific DNA N6-adenine methyltransferases. Single-molecule long-read sequencing of chromatin stencils enabled nucleotide-resolution readout of the primary architecture of multikilobase chromatin fibers (Fiber-seq). Fiber-seq exposed widespread plasticity in the linear organization of individual chromatin fibers and illuminated principles guiding regulatory DNA actuation, the coordinated actuation of neighboring regulatory elements, single-molecule nucleosome positioning, and single-molecule transcription factor occupancy. Our approach and results open new vistas on the primary architecture of gene regulation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cromatina
/
Regulação da Expressão Gênica
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Montagem e Desmontagem da Cromatina
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Sequenciamento de Nucleotídeos em Larga Escala
/
Imagem Individual de Molécula
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article