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| Pàgina inicial > Articles > Articles publicats > A complex interplay between H2A.Z and HP1 isoforms regulates pericentric heterochromatin |
(Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut de Recerca I Innovació en Ciències de La Vida i de La Salut a La Catalunya Central) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia) (Centro de Investigación Biomédica en Red de Enfermedades Raras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
| Data: | 2023 |
| Resum: | 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. |
| Ajuts: | Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR148 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021SGR01378 Agència de Gestió d'Ajuts Universitaris i de Recerca 2022FI_B00924 European Commission. Horizon 2020 895979 Agencia Estatal de Investigación PID2020-117284RB-I00 Agencia Estatal de Investigación SAF2017-88975R |
| Nota: | The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2017-88975R, PID2020-117284RB-I00) (AV), and cofounded by FEDER funds/European Regional Development Fund (ERDF)-A Way to Build Europe; the Catalan Government Agency AGAUR (2017-SGR-148, 2021-SGR-01378 to AV) (FI-AGAUR fellowship 2022 FI_B 00924 to AG-S). We also thank the CERCA Programme/Generalitat de Catalunya for institutional support. Work from the PS lab is funded by Nazarbayev University Faculty Development Grant 021220FD2451. The work was also supported by the European Commission's Horizon 2020 research and innovation programme (BNV; Marie Słodowska-Curie grant # 895979). |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | HP1α ; β ; Heterochromatin ; 2A.Z ; Zepigenetics ; Genome stability ; H3K9me3 ; H4K20me3 |
| Publicat a: | Frontiers in Cell and Developmental Biology, Vol. 11 (2023) , p. 1293122, ISSN 2296-634X |
