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La histona H2B ubicuitada químicamente estimula la metilación intranucleosómica mediada por hDot1L
Robert K McGinty1, Jaehoon Kim, Champak Chatterjee
1Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, New York 10065, USA.
Nature
|May 2, 2008
Resumen
La ubiquitilación de la histona H2B (uH2B) estimula directamente la metilación de H3 K79 por hDot1L, revelando un mecanismo de cruce directo. Este hallazgo aclara la función de uH2B en las vías de modificación de histonas y la regulación del genoma.
Área de la Ciencia:
- La epigenética y la biología molecular.
- Biología de la cromatina Biología de la cromatina
- Modificaciones después de la traducción.
Sus antecedentes:
- La hipótesis del "código histónico" postula que las modificaciones de la histona regulan la expresión del genoma.
- La ubicuidad de la histona (uH2B) está vinculada a la metilación de la histona H3 K79, pero su papel específico no está claro.
Objetivo del estudio:
- Para dilucidar la función directa de uH2B en el cruce con la metilación H3 K79.
- Demostrar el mecanismo bioquímico subyacente a la interacción entre la metilación de uH2B y H3 K79.
Principales métodos:
- La ubicuidad química específica del sitio de la histona H2B utilizando la ligación de proteínas expresadas (EPL).
- Reconstitución del H2B ubicuitado en nucleosomas definidos.
- Ensayos bioquímicos para medir la metilación H3 K79 por el humano Dot1-like (hDot1L).
Principales resultados:
- El H2B químicamente ubicuitado estimula directamente la metilación mediada por hDot1L de H3 K79.
- La estimulación está mediada por el dominio catalítico de hDot1L, probablemente a través de efectos alostéricos.
- uH2B mejora la metilación específicamente dentro de los nucleosomas que contienen la modificación.
Conclusiones:
- Este estudio demuestra un cruce bioquímico directo entre la metilación de uH2B y H3 K79 dentro del nucleosoma.
- uH2B actúa como un activador directo de la metilación de H3 K79 por hDot1L.
- Los hallazgos proporcionan una visión mecanicista de la modificación de histonas y su papel en la regulación del genoma.
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These groups modify specific amino acids in a protein.
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Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
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02:32Histone Modification
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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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Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...