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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Represión transcripcional mediada por el reposicionamiento de genes en la lámina nuclear
K L Reddy1, J M Zullo, E Bertolino
1Howard Hughes Medical Institute, The University of Chicago, GCIS W522, 929 East 57th Street, Chicago, Illinois 60637, USA.
Nature
|February 15, 2008
Resumen
El posicionamiento de genes en la lámina nuclear puede reprimir la actividad génica. Este estudio demuestra que los genes atados a la membrana nuclear interna (INM) conducen a la represión transcripcional, lo que afecta la regulación de los genes.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- La compartimentación nuclear juega un papel clave en la regulación de la expresión génica en los metazoos.
- El posicionamiento de genes, como los loci de la inmunoglobulina, en la lámina nuclear se correlaciona con la represión génica, pero las consecuencias funcionales no se han probado en gran medida.
Objetivo del estudio:
- Investigar las consecuencias funcionales del posicionamiento génico en la membrana nuclear interna (MNI).
- Para determinar si los genes de atadura al INM afectan su actividad transcripcional.
Principales métodos:
- Desarrolló un sistema de atadura inducible para posicionar genes en el INM en fibroblastos de ratón.
- Utilizó ADN-immunoFISH tridimensional para visualizar regiones cromosómicas.
- Empleó metilación dirigida de la adenina (DamID) para evaluar las interacciones moleculares.
Principales resultados:
- Reposicionamiento demostrado de las regiones cromosómicas a la lámina nuclear, dependiente de la dinámica de la envoltura nuclear durante la mitosis.
- Se demostró que los genes de atadura al INM conducen a la acumulación de proteínas laminas e INM.
- Se confirmó que el reclutamiento de genes para el INM puede resultar en represión transcripcional.
- Se encontró que los loci inactivos de inmunoglobulina en la periferia nuclear interactúan con las proteínas INM y la lámina.
Conclusiones:
- El reclutamiento de genes en la membrana nuclear interna puede conducir a la represión transcripcional.
- Las interacciones moleculares entre los loci de la inmunoglobulina y las proteínas INM/lamina pueden compartimentar estos loci, limitando el acceso a los factores de transcripción y recombinación.
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