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TET2 promueve la O-GlcNAcilación de la histona durante la transcripción génica

Qiang Chen¹, Yibin Chen, Chunjing Bian

¹Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.

|December 11, 2012

Resumen

Diez de once enzimas de translocación (TET) regulan la transcripción génica. Este estudio revela que TET2 interactúa con la transferasa β-N-acetilglucosamina (O-GlcNAc) ligada a O (OGT), descubriendo un mecanismo de O-GlcNAcilación de la cromatina dependiente de TET2 para la regulación génica.

Área de la Ciencia:

La epigenética es la epigenética.
Biología Molecular Biología Molecular
La bioquímica es la bioquímica.

Sus antecedentes:

Diez de las once enzimas de translocación (TET) (TET1, TET2, TET3) modifican el ADN mediante la conversión de 5-metilcitocina en 5-hidroximetilcitocina.
Los mecanismos moleculares precisos por los cuales las enzimas TET regulan la transcripción génica no se comprenden completamente.

Objetivo del estudio:

Para identificar los socios funcionales de las proteínas TET.
Para dilucidar los mecanismos moleculares de la regulación de la transcripción génica mediada por TET.

Principales métodos:

Purificación de la afinidad proteica para identificar los interactores de la proteína TET.
Análisis de la interacción TET2-OGT y su efecto sobre la asociación de la cromatina y la modificación de la histona.
Investigando el papel de TET2 y O-GlcNAcilación en los sitios de inicio de la transcripción.

Principales resultados:

Se encontró que TET2 y TET3 se asocian con la transferasa β-N-acetilglucosamina (O-GlcNAc) vinculada a O (OGT).
TET2 interactúa directamente con la OGT, facilitando la asociación de la cromatina de la OGT y la O-GlcNAcilación de la histona dependiente de la OGT.
TET2 y OGT co-localizan en los sitios de inicio de la transcripción, y la regulación a la baja de TET2 impacta las marcas de histona O-GlcNAc cruciales para la transcripción.

Conclusiones:

Se ha identificado una nueva O-GlcNAcilación de la cromatina dependiente de TET2.
TET2 y OGT coordinan las modificaciones epigenéticas duales en el ADN y las histonas para regular la transcripción génica.

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