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Maintaining oxidized H3 in heterochromatin is required for the oncogenic capacity of triple-negative breast cancer cells

by Viaplana, Cristina , Dienstmann, Rodrigo , Vincente Peg , Blanco, Enrique , Cigliano, Riccardo Aiese , Luciano Di Croce , Pascual-Reguant, Laura , Saura, Cristina , Antonio García De Herreros , Jerónimo, Celia , Simonetti, Sara , Morancho, Beatriz , Verde, Gaetano , Nuciforo, Paolo , Segura-Bayona, Sandra , Serra-Bardenys, Gemma , Tian, Tian V , Joaquín Arribas , Escorihuela, Marta , Villanueva, Josep , Millanes-Romero, Alba , Stracker, Travis H , Querol, Jessica , Sandra Peiró

in Breast cancer / Cancer Biology / Chromatin / Heterochromatin / Histone H2A / Lysine / Lysyl oxidase / Ubiquitin-protein ligase / Ubiquitination

2020

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Maintaining oxidized H3 in heterochromatin is required for the oncogenic capacity of triple-negative breast cancer cells

in Breast cancer / Cancer Biology / Chromatin / Heterochromatin / Histone H2A / Lysine / Lysyl oxidase / Ubiquitin-protein ligase / Ubiquitination

2020

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Maintaining oxidized H3 in heterochromatin is required for the oncogenic capacity of triple-negative breast cancer cells

in Breast cancer / Cancer Biology / Chromatin / Heterochromatin / Histone H2A / Lysine / Lysyl oxidase / Ubiquitin-protein ligase / Ubiquitination

2020

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Paper

Maintaining oxidized H3 in heterochromatin is required for the oncogenic capacity of triple-negative breast cancer cells

Viaplana, Cristina,

Dienstmann, Rodrigo,

Vincente Peg,

Blanco, Enrique,

Cigliano, Riccardo Aiese,

Luciano Di Croce,

Pascual-Reguant, Laura,

Saura, Cristina,

Antonio García De Herreros,

Jerónimo, Celia,

Simonetti, Sara,

Morancho, Beatriz,

Verde, Gaetano,

Nuciforo, Paolo,

Segura-Bayona, Sandra,

Serra-Bardenys, Gemma,

Tian, Tian V,

Joaquín Arribas,

Escorihuela, Marta,

Villanueva, Josep,

Millanes-Romero, Alba,

Stracker, Travis H,

Querol, Jessica,

Sandra Peiró

2020

Overview

The histone modification of H3 oxidized at lysine 4 (H3K4ox) is catalyzed by lysyl oxidase-like 2 (LOXL2) and is enriched in heterochromatin in triple-negative breast cancer (TNBC) cells. Although H3K4ox has been linked to the maintenance of compacted chromatin, the molecular mechanism underlying this maintenance is unknown. Here we show that H3K4ox is read by the CRL4B complex, leading to the ubiquitination of histone H2A through the E3 ligase RBX1. Finally, interactions between RUVBL1/2 and LOXL2 are involved in the incorporation of the histone variant H2A.Z, which plays an essential role in the mechanism controlling the dynamics of oxidized H3. Maintenance of H3K4ox in chromatin is essential for heterochromatin properties, and disruption of any of the members involved in this pathway blocks the oncogenic properties of TNBC cells.

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Publisher

Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory

Subject

/ Lysine