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H3K27me3 heredado por la línea germinal restringe la función del potenciador durante la transición materna a cigótica

Fides Zenk^1,2, Eva Loeser¹, Rosaria Schiavo¹

¹Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, D-79108 Freiburg, Germany.

Science (New York, N.Y.)

|July 15, 2017

Resumen

Las marcas epigenéticas maternas, como H3K27me3, son cruciales para el desarrollo de la descendencia. Esta marca histónica represiva, propagada por factores maternos, previene errores de desarrollo y asegura la activación genética adecuada.

Área de la Ciencia:

Epigenética y biología del desarrollo
Los mecanismos moleculares de la herencia

Sus antecedentes:

Las modificaciones epigenéticas en los gametos se pueden heredar, lo que influye en el desarrollo de la descendencia.
Los mecanismos y consecuencias de la herencia epigenética transgeneracional siguen siendo en gran medida desconocidos.
Las modificaciones de la histona juegan un papel clave en la regulación de la expresión génica y la herencia.

Objetivo del estudio:

Investigar el papel de las marcas epigenéticas maternas en el desarrollo embrionario temprano.
Para aclarar los mecanismos moleculares por los cuales la memoria epigenética se transmite a través de generaciones.
Para entender las consecuencias de interrumpir la información epigenética heredada por la línea germinal.

Principales métodos:

Estudió la herencia de la marca histónica represiva H3K27me3 en ovocitos de *Drosophila* y embriones tempranos.
Se investigó el papel del potenciador materno de zeste (E(z), el componente 2 del complejo represivo de Polycomb, en la propagación de H3K27me3.
Se analizó el impacto de la herencia H3K27me3 interrumpida en las marcas histónicas (H3K27ac) y la activación génica durante la activación del genoma cigótico.

Principales resultados:

Los ovocitos de *Drosophila* transmiten la marca de histona represiva H3K27me3 a la descendencia.
El potenciador materno del apetito es esencial para la propagación de H3K27me3 en la embriogénesis temprana.
El H3K27me3 heredado por la línea germinal previene la acumulación aberrante de H3K27ac y la activación precoz del gen, crucial para el desarrollo.
La interrupción de esta memoria epigenética conduce a la letalidad embrionaria, insalvable por el restablecimiento posterior del gen cigótico.

Conclusiones:

El H3K27me3 heredado por la madre, propagado por el Enhancer de zeste materno, es vital para el desarrollo embrionario temprano.
Esta memoria epigenética regula la actividad del potenciador y la activación del gen específico del linaje durante la activación del genoma cigótico.
Si no se mantiene la información epigenética heredada de la línea germinal, se produce un fallo del desarrollo.

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