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La acetilación en el dominio globular de la histona H3 regula la expresión génica en las levaduras
Feng Xu1, Kangling Zhang, Michael Grunstein
1Department of Biological Chemistry, Geffen School of Medicine at UCLA, and the Molecular Biology Institute, University of California-Los Angeles, Boyer Hall, Los Angeles, CA 90095, USA.
Cell
|May 11, 2005
Resumen
La acetilación de la histona H3 lisina 56, un nuevo sitio en el dominio globular, regula la actividad génica mediante el reclutamiento del complejo SWI / SNF. Este proceso es crucial para la activación de los genes, en particular los que codifican las histonas, en Saccharomyces cerevisiae.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La epigenética es la epigenética.
- Genética de la levadura Genética de la levadura
Sus antecedentes:
- La acetilación de la histona ocurre típicamente en las colas N-terminales, regulando la actividad génica.
- La estructura del núcleo del nucleosoma juega un papel crítico en la accesibilidad del ADN y la regulación de los genes.
Objetivo del estudio:
- Para identificar y caracterizar nuevos sitios de acetilación de histonas.
- Para investigar el papel de la acetilación de la histona H3 lisina 56 (K56) en la regulación génica.
- Para dilucidar el mecanismo por el cual la acetilación de K56 influye en la transcripción génica.
Principales métodos:
- Mutagénesis dirigida al sitio para estudiar la histona H3 K56.
- Análisis de los patrones de expresión génica en Saccharomyces cerevisiae.
- Inmunoprecipitación de la cromatina para evaluar las interacciones proteína-ADN.
- Pruebas bioquímicas para determinar la función de SPT10 y Snf5.5.
Principales resultados:
- Identificó la lisina 56 (K56) en la histona H3 como un nuevo sitio de acetilación ubicado en el dominio globular.
- La acetilación de K56 se enriquece preferentemente en genes activos, incluidos los genes de histona.
- SPT10, una presunta acetiltransferasa, es esencial para la acetilación específica del ciclo celular de K56 en los genes de la histona.
- La acetilación de la histona H3 K56 facilita el reclutamiento de la subunidad Snf5 del complejo de remodelación de nucleosomas SWI/SNF.
Conclusiones:
- La acetilación de la histona H3 K56 actúa como un mecanismo regulador en el sitio de entrada-salida del nucleosoma.
- Este evento de acetilación es crucial para reclutar el complejo SWI / SNF, regulando así la actividad génica.
- Los hallazgos revelan una nueva capa de control epigenético sobre la expresión génica en la levadura.
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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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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...
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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,...
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