A complex interplay between H2A.Z and HP1 isoforms regulates pericentric heterochromatin

Pericentric heterochromatin (PCH) plays an essential role in the maintenance of genome integrity and alterations in PCH have been linked to cancer and aging. HP1 α, β, and γ, are hallmarks of constitutive heterochromatin that are thought to promote PCH structure through binding to heterochromatin-sp...

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Detalhes bibliográficos
Autores: González Miranda, Jessica|||0000-0001-7732-1564, Bosch-Presegué, Laia|||0000-0001-8025-2416, Marazuela Duque, Anna|||0000-0001-6787-8668, Guitart-Solanes, Anna, Espinosa-Alcantud, María Dolores|||0000-0002-1126-2458, Fernandez, Agustín F., Brown, Jeremy P., Ausió, Juan, Vazquez Prat, Berta Nieves|||0000-0002-8164-3926, Singh, Prim B., Fraga, Mario|||0000-0001-8450-2603, Vaquero, Alejandro|||0000-0002-8735-4156
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:289562
Acesso em linha:https://ddd.uab.cat/record/289562
https://dx.doi.org/urn:doi:10.3389/fcell.2023.1293122
Access Level:acceso abierto
Palavra-chave:HP1α
β
Heterochromatin
2A.Z
Zepigenetics
Genome stability
H3K9me3
H4K20me3
Descrição
Resumo:Pericentric heterochromatin (PCH) plays an essential role in the maintenance of genome integrity and alterations in PCH have been linked to cancer and aging. HP1 α, β, and γ, are hallmarks of constitutive heterochromatin that are thought to promote PCH structure through binding to heterochromatin-specific histone modifications and interaction with a wide range of factors. Among the less understood components of PCH is the histone H2A variant H2A.Z, whose role in the organization and maintenance of PCH is poorly defined. Here we show that there is a complex interplay between H2A.Z and HP1 isoforms in PCH. While the loss of HP1α results in the accumulation of H2A.Z.1 in PCH, which is associated with a significant decrease in its mobile fraction, H2A.Z.1 binds preferentially to HP1β in these regions. Of note, H2A.Z.1 downregulation results in increased heterochromatinization and instability of PCH, reflected by accumulation of the major epigenetic hallmarks of heterochromatin in these regions and increased frequency of chromosome aberrations related to centromeric/pericentromeric defects. Our studies support a role for H2A.Z in genome stability and unveil a key role of H2A.Z in the regulation of heterochromatin-specific epigenetic modifications through a complex interplay with the HP1 isoforms.

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