LATS kinase-mediated CTCF phosphorylation and selective loss of genomic binding.
Sci Adv
; 6(8): eaaw4651, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-32128389
ABSTRACT
Chromatin topological organization is instrumental in gene transcription. Gene-enhancer interactions are accommodated in the same CTCF-mediated insulated neighborhoods. However, it remains poorly understood whether and how the 3D genome architecture is dynamically restructured by external signals. Here, we report that LATS kinases phosphorylated CTCF in the zinc finger (ZF) linkers and disabled its DNA-binding activity. Cellular stress induced LATS nuclear translocation and CTCF ZF linker phosphorylation, and altered the landscape of CTCF genomic binding partly by dissociating it selectively from a small subset of its genomic binding sites. These sites were highly enriched for the boundaries of chromatin domains containing LATS signaling target genes. The stress-induced CTCF phosphorylation and locus-specific dissociation from DNA were LATS-dependent. Loss of CTCF binding disrupted local chromatin domains and down-regulated genes located within them. The study suggests that external signals may rapidly modulate the 3D genome by affecting CTCF genomic binding through ZF linker phosphorylation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Fator de Ligação a CCCTC
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article