Video Experimental Relacionado
Updated: Jun 19, 2026
11:02
Complete Workflow for Analysis of Histone Post-translational Modifications Using Bottom-up Mass Spectrometry: From Histone Extraction to Data Analysis
Published on: May 17, 2016
El cruce de histonas entre H3S10ph y H4K16ac genera un código de histonas que media el alargamiento de la
Alessio Zippo1, Riccardo Serafini, Marina Rocchigiani
1Dipartimento di Biologia Molecolare Università di Siena, Siena, Italy.
Cell
|September 22, 2009
Resumen
La fosforilación de la histona H3 en la serina 10 (H3S10ph) inicia una cascada que activa la transcripción del gen FOSL1. Esto involucra a la quinasa PIM1, 14-3-3, MOF y BRD4, lo que lleva a una mayor procesividad de la ARN polimerasa II.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La epigenética es la epigenética.
- Reglamento genético Reglamento genético.
Sus antecedentes:
- Las modificaciones de las histonas, como la fosforilación y la acetilación, juegan un papel crucial en la regulación de la transcripción génica.
- La fosforilación de la histona H3 en la serina 10 (H3S10ph) está relacionada con la activación transcripcional, pero los mecanismos moleculares precisos siguen siendo incompletamente comprendidos.
Objetivo del estudio:
- Para dilucidar el mecanismo molecular por el cual H3S10ph desencadena el alargamiento de transcripción del gen FOSL1.
- Para identificar las proteínas clave y las modificaciones de histonas involucradas en esta cascada de señalización.
Principales métodos:
- Investigó el papel de la quinasa PIM1 en la fosforilación de la histona H3 en el potenciador FOSL1.
- Utilizado co-inmunoprecipitación y ensayos bioquímicos para identificar las interacciones entre 14-3-3, MOF, y BRD4.
- Se analizaron las modificaciones histónicas (H3S10ph, H4K16ac) y su impacto en el alargamiento de la transcripción utilizando inmunoprecipitación de cromatina y secuenciación de ARN.
Principales resultados:
- La estimulación sérica activa la quinasa PIM1 para fosforilar la histona H3 preacetilada en el potenciador de FOSL1.
- La proteína adaptadora 14-3-3 se une a los nucleosomas H3S10ph y recluta a la histona acetiltransferasa MOF, lo que lleva a H4K16ac.ac.
- Este cruce de histonas crea un código H3K9acS10ph / H4K16ac, reclutando BRD4 y posteriormente P-TEFb, que libera la ARN polimerasa II en pausa para una mayor elongación.
Conclusiones:
- H3S10ph actúa como un disparador crítico para el alargamiento transcripcional del gen FOSL1.
- Una cascada secuencial que involucra a PIM1, 14-3-3, MOF y BRD4 media la transcripción inducida por H3S10ph.
- El estudio revela un nuevo código de reconocimiento nucleosómico (H3K9acS10ph/H4K16ac) esencial para reclutar factores de alargamiento de la transcripción.
Más Videos Relacionados
10:09Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
10:28Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Videos de Conceptos Relacionados
02:10The Nucleosome Core Particle
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.
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
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.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:25Spreading of Chromatin Modifications
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.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
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...
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...
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.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
01:12The Nucleosome Core Particle
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...