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Proteoma y genoma definidos por la marca de acilación de la cromatina en células vivas

Fangfei Qin¹, Boyuan Li², Hui Wang²

¹Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy of Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Shenzhen Bay Laboratory, Shenzhen 518055, China.

|March 3, 2023

Resumen

Desarrollamos una nueva estrategia SiTomics para mapear las modificaciones histónicas en las células vivas. Este enfoque vincula los metabolitos a los cambios de la cromatina, revelando nuevos conocimientos sobre la regulación génica y las interacciones de las proteínas.

Área de la Ciencia:

La bioquímica
Biología molecular
La epigenética

Sus antecedentes:

El mapeo de las modificaciones dinámicas de las histonas en las células vivas es un desafío.
Se necesita una estrategia generalizable para el perfilado de la cromatina in situ específico del sitio.

Objetivo del estudio:

Desarrollar una estrategia multiómica con resolución en un solo sitio (SiTomics) para mapear las modificaciones dinámicas de las histonas.
Para perfilar el proteoma cromatinizado y el genoma definido por acilaciones específicas de cromatina en células vivas.

Principales métodos:

Aprovechó la expansión del código genético para el desarrollo del kit de herramientas SiTomics.
Células estimuladas con ácidos grasos de cadena corta para observar las modificaciones histónicas.
Datos multiómicos integrados para vincular las modificaciones al proteoma, genoma y función.

Principales resultados:

Se reveló una crotonilación (H3K56cr) y una β-hidroxibutirilación (H3K56bhb) distintas tras la estimulación.
Identificó GLYR1 como una proteína que modula la localización de H3K56cr.
Descubrió un repertorio elevado de superpotenciadores vinculados a la β-hidroxibutirilación.

Conclusiones:

SiTomics permite el mapeo sistemático de las modificaciones dinámicas y el perfil de la cromatina.
Se establecieron vínculos entre las marcas de acilación de la cromatina, el proteoma, el genoma y las funciones celulares.
SiTomics es una plataforma para diseccionar los ejes "metabolitos-modificación-regulación" más allá de las histonas.

Palabras clave:

Cromatina y sus derivados Crotonilación regulación genética Expansión del código genético Marca de histonas Los metabolitos multiómica Modificación después de la traducción el superpotenciador Deshidratación de los ácidos grasos

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