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Published on: September 20, 2018
Papel de la proteína policomb EED en la propagación de las marcas histónicas represivas
Raphael Margueron1, Neil Justin, Katsuhito Ohno
1Howard Hughes Medical Institute and Department of Biochemistry, New York University Medical School, 522 First Avenue, New York, New York 10016, USA.
Nature
|September 22, 2009
Resumen
La proteína EED en el Complejo Represivo Polycomb 2 (PRC2) se une a las marcas histónicas represivas, activando su actividad de silenciamiento de genes. Este mecanismo ayuda a mantener los estados de la cromatina y transmite información epigenética durante la división celular.
Área de la Ciencia:
- La epigenética es la epigenética.
- Biología Molecular Biología Molecular
- Biología del desarrollo Biología del desarrollo.
Sus antecedentes:
- Las proteínas del grupo de policombos mantienen estados cromatínicos represivos.
- El Complejo Represivo Polycomb 2 (PRC2) media en el silenciamiento de genes a través de la trimetilación de la histona H3 lisina 27 (H3K27me3).
- EZH2, SUZ12 y EED son subunidades clave de PRC2.2.
Objetivo del estudio:
- Investigar el papel de la subunidad EED en la actividad de PRC2.
- Para aclarar el mecanismo por el cual PRC2 reconoce y propaga las marcas de cromatina represiva.
Principales métodos:
- Ensayos bioquímicos para estudiar las interacciones de la cola de EED-histona.
- Ensayos in vitro de la actividad de la metiltransferasa de PRC2.2.
- Manipulación genética de EED en Drosophila para evaluar el impacto en el desarrollo.
Principales resultados:
- El dominio carboxiterminal de EED se une a los residuos de lisina trimetilada en las colas de histona.
- Esta unión activa alostéricamente la actividad de la metiltransferasa de PRC2.2.
- Las mutaciones en EED que interrumpen la unión a la trimetil-lisina eliminan la activación de PRC2 y conducen a defectos de desarrollo en Drosophila.
Conclusiones:
- El EED actúa como un sensor para las marcas de cromatina represiva, activando el PRC2.
- Este mecanismo es crucial para la propagación y el mantenimiento de las marcas H3K27me3.
- Los hallazgos proponen un modelo para la transmisión de la memoria epigenética durante la división celular.
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02:32Position-effect Variegation
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
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01:01Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
01:01Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...