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Oligomerización de CtBP1/2 Promueve la Represión Transcripcional Mediada por G9a

Bin Zhang¹, Junheng Jiang¹, Wenxin Sun¹

¹School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen 361102, China.

The Journal of biological chemistry

|December 19, 2025

Resumen

Los correpresores CtBP1/2 se unen a la metiltransferasa G9a, mejorando su actividad. Este complejo regula la expresión génica en células de cáncer colorrectal, ofreciendo una diana terapéutica potencial.

Área de la Ciencia:

Biología Molecular
Epigenética
Investigación del Cáncer

Sus antecedentes:

Los correpresores CtBP1 y CtBP2 (CtBP1/2) regulan la expresión génica reclutando modificadores de cromatina.
La base estructural de la represión transcripcional mediada por CtBP1/2 no se comprende bien.

Objetivo del estudio:

Elucidar la base estructural de la represión génica mediada por CtBP1/2.
Investigar la interacción entre CtBP1/2 y la metiltransferasa de histonas G9a.

Principales métodos:

Cristalografía de rayos X
Ensayos bioquímicos
Estudios celulares en modelos de carcinoma colorrectal (CCRC)

Principales resultados:

Los tetrámeros de CtBP1/2 interactúan directamente con G9a a través de un motivo en el dominio pre-SET de G9a.
Esta interacción mejora la actividad catalítica de G9a, dependiente de la oligomerización de CtBP1/2.
La interrupción de la interfaz CtBP2-G9a en células de CCRC reduce H3K9me2, regula al alza PTEN e inhibe la proliferación.

Conclusiones:

Se establece un marco estructural para la regulación de la actividad de G9a por CtBP1/2.
El complejo CtBP1/2-G9a es una diana terapéutica potencial para el cáncer colorrectal.

Palabras clave:

CtBP1/2 G9a estructura cristalina epigenética silenciamiento génico metiltransferasa de histonas oligomerización de proteínas

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