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Regulación de la unión de la HP1-cromatina mediante la metilación y fosforilación de la histona H3
Wolfgang Fischle1, Boo Shan Tseng, Holger L Dormann
1Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA. fischlw@rockefeller.edu
Nature
|October 14, 2005
Resumen
La metilación de la histona H3 lisina 9 recluta a la heterocromatina proteína 1 (HP1). Sin embargo, la fosforilación de H3 serina 10 durante la fase M expulsa HP1, revelando un nuevo mecanismo de regulación epigenética.
Área de la Ciencia:
- La epigenética y la biología molecular.
- El Reglamento del Ciclo Celular.
- Dinámica de la cromatina Dinámica de la cromatina Dinámica de la cromatina Dinámica de la cromatina Dinámica de la cromatina Dinámica de la cromatina Dinámica de la cromatina Dinámica de la cromatina Dinámica de la cromatina Dinámica de la cromatina Dinámica de la cromatina
Sus antecedentes:
- La tri-metilación de la histona H3 lisina 9 (H3K9me3) es crucial para la unión de la heterocromatina a la proteína 1 (HP1) y el silenciamiento de genes.
- Las proteínas HP1 son esenciales para el envasado de la cromatina y la formación de heterocromatina.
- Comprender la dinámica de HP1 durante el ciclo celular es clave para comprender la regulación génica.
Objetivo del estudio:
- Investigar el mecanismo de liberación de HP1 de la cromatina durante la fase M.
- Para aclarar el papel de las modificaciones histónicas en la regulación de la disociación HP1.
- Identificar los factores clave involucrados en la dinámica de HP1 durante la mitosis.
Principales métodos:
- Inmunoprecipitación de la cromatina (ChIP) para evaluar los niveles de HP1 y la modificación de la histona.
- Análisis del ciclo celular y preparación del cromosoma mitótico.
- La inhibición y el agotamiento de las quinasas específicas, tales como Aurora B.
Principales resultados:
- HP1alpha, -beta y -gamma se liberan de la cromatina durante la fase M a pesar de los niveles estables de H3K9me3.
- La fosforilación de la histona H3 serina 10 (H3S10ph), adyacente a H3K9me3, es suficiente para desplazar a HP1.1.
- La inhibición de la Aurora B quinasa previene la disociación de HP1, lo que confirma la necesidad de H3S10ph para la liberación de HP1.
Conclusiones:
- H3S10ph es una modificación crítica y transitoria que media la eyección de HP1 de la cromatina durante la fase M.
- La interacción entre el H3K9me3 estable y el H3S10ph dinámico gobierna las interacciones HP1-cromatina.
- Esta lectura combinatoria de modificaciones post-traducionales adyacentes representa un nuevo mecanismo regulador en la expresión génica dependiente del ciclo celular.
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02:04Covalently Linked Protein Regulators
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These groups modify specific amino acids in a protein.
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02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
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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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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.
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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.
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02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...