Dual-role transcription factors stabilize intermediate expression levels.
Cell
; 187(11): 2746-2766.e25, 2024 May 23.
Article
en En
| MEDLINE
| ID: mdl-38631355
ABSTRACT
Precise control of gene expression levels is essential for normal cell functions, yet how they are defined and tightly maintained, particularly at intermediate levels, remains elusive. Here, using a series of newly developed sequencing, imaging, and functional assays, we uncover a class of transcription factors with dual roles as activators and repressors, referred to as condensate-forming level-regulating dual-action transcription factors (TFs). They reduce high expression but increase low expression to achieve stable intermediate levels. Dual-action TFs directly exert activating and repressing functions via condensate-forming domains that compartmentalize core transcriptional unit selectively. Clinically relevant mutations in these domains, which are linked to a range of developmental disorders, impair condensate selectivity and dual-action TF activity. These results collectively address a fundamental question in expression regulation and demonstrate the potential of level-regulating dual-action TFs as powerful effectors for engineering controlled expression levels.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Año:
2024
Tipo del documento:
Article
País de afiliación:
China