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Lid2 es necesario para coordinar las metilaciones H3K4 y H3K9 de la heterocromatina y la euchromatina
Fei Li1, Maite Huarte, Mikel Zaratiegui
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. feili@nature.berkeley.edu
Cell
|October 30, 2008
Resumen
La proteína Lid2 del dominio JmjC actúa como una histona H3 lisina-4 (H3K4) desmetilasa, crucial para la formación de heterocromatina y el silenciamiento de genes. Lid2 vincula la desmetilación de H3K4 con la metilación de H3K9, coordinando la regulación de la cromatina.
Área de la Ciencia:
- La epigenética es la epigenética.
- Biología de la cromatina Biología de la cromatina
- Biología Molecular Biología Molecular
Sus antecedentes:
- Los patrones de metilación de las histonas, específicamente la metilación H3K9 y H3K4, son críticos para definir la heterocromatina y la euchromatina, respectivamente.
- Estas modificaciones dictan la arquitectura de la cromatina y la regulación de la expresión génica en los eucariotas.
Objetivo del estudio:
- Para identificar la función de la proteína Lid2 del dominio JmjC en S. pombe.
- Para aclarar el papel de Lid2 en la regulación de la metilación de histonas y su impacto en la estructura de la cromatina.
Principales métodos:
- Pruebas bioquímicas para determinar la actividad enzimática de Lid2 como una desmetilasa.
- Análisis genético de la función de Lid2 en la formación y silenciamiento de la heterocromatina.
- Investigando las interacciones proteína-proteína entre Lid2, Clr4 y el complejo Dos1/Clr8-Rik1.
Principales resultados:
- Lid2 fue identificado como una desmetilasa trimetilo H3K4 responsable de la hipometilación de H3K4 en la heterocromatina.
- Lid2 interactúa física y funcionalmente con la H3K9 metiltransferasa Clr4 a través del complejo Dos1/Clr8-Rik1.
- La interrupción del dominio JmjC de Lid2 causó defectos de heterocromatina y agotamiento del siRNA, mientras que la sobreexpresión de Lid2 aumentó el silenciamiento.
- Lid2 también se requiere para la regulación cruzada de la metilación de H3K4 y H3K9 en euchromatin.
Conclusiones:
- Lid2 juega un doble papel en la coordinación de la metilación de H3K4 y H3K9 para la formación adecuada de heterocromatina y el silenciamiento de genes.
- Los hallazgos revelan un vínculo mecánico entre la desmetilación de H3K4 y la metilación de H3K9, destacando la regulación epigenética coordinada.
- Es probable que la actividad de Lid2 en la eucromatina esté modulada por interacciones dinámicas con otras enzimas modificadoras de histonas.
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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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01:01Euchromatin
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Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
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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.
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.
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