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ASB7 es un regulador negativo de la homeostasis de H3K9me3

Liwen Zhou¹, Zhenxuan Chen¹, Yezi Zou²

¹Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.

Science (New York, N.Y.)

|May 29, 2025

Resumen

Un nuevo estudio identifica a ASB7 como un regulador clave de la homeostasis de la trimetilación de la histona H3 lisina 9 (H3K9me3). Este hallazgo revela un circuito dinámico que controla la herencia epigenética y previene la formación excesiva de heterocromatina.

Área de la Ciencia:

La epigenética
Biología de la cromatina
Biología molecular

Sus antecedentes:

El mantenimiento de la trimetilación de histona H3 lisina 9 (H3K9me3) implica un ciclo de retroalimentación positiva.
Los mecanismos que restringen esta retroalimentación para la homeostasis de H3K9me3 son poco conocidos.

Objetivo del estudio:

Para identificar nuevos reguladores de la homeostasis de H3K9me3.
Para aclarar los mecanismos moleculares que rigen la dinámica de H3K9me3.

Principales métodos:

Espectrometría CRISPR-Cas9 a escala genómica.
Identificación de la ubiquitina ligasa CUL5^ASB7 E3.
Análisis de las interacciones proteína-proteína y vías de degradación.

Principales resultados:

ASB7 actúa como un regulador negativo de H3K9me3 promoviendo la degradación de SUV39H1.
HP1 recluta ASB7 para la heterocromatina.
La fosforilación de CDK1 de ASB7 durante la mitosis previene la degradación de SUV39H1, restaurando el H3K9me3.

Conclusiones:

Un circuito dinámico que involucra a HP1, SUV39H1 y ASB7 regula la homeostasis de H3K9me3.
Este circuito asegura una herencia epigenética fiel.
Los resultados previenen la formación excesiva de heterocromatina.

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