Polymerization of ZBTB transcription factors regulates chromatin occupancy.
Mol Cell
; 84(13): 2511-2524.e8, 2024 Jul 11.
Article
en En
| MEDLINE
| ID: mdl-38996460
ABSTRACT
BCL6, an oncogenic transcription factor (TF), forms polymers in the presence of a small-molecule molecular glue that stabilizes a complementary interface between homodimers of BCL6's broad-complex, tramtrack, and bric-à-brac (BTB) domain. The BTB domains of other proteins, including a large class of TFs, have similar architectures and symmetries, raising the possibility that additional BTB proteins self-assemble into higher-order structures. Here, we surveyed 189 human BTB proteins with a cellular fluorescent reporter assay and identified 18 ZBTB TFs that show evidence of polymerization. Through biochemical and cryoelectron microscopy (cryo-EM) studies, we demonstrate that these ZBTB TFs polymerize into filaments. We found that BTB-domain-mediated polymerization of ZBTB TFs enhances chromatin occupancy within regions containing homotypic clusters of TF binding sites, leading to repression of target genes. Our results reveal a role of higher-order structures in regulating ZBTB TFs and suggest an underappreciated role for TF polymerization in modulating gene expression.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cromatina
/
Microscopía por Crioelectrón
Límite:
Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article