The role of Smarcad1 in retroviral repression in mouse embryonic stem cells.

Embryonic stem cells Epigenetic silencing H3.3 Retrovirus Smarcad1 Trim28

Journal

Mobile DNA
ISSN: 1759-8753
Titre abrégé: Mob DNA
Pays: England
ID NLM: 101519891

Informations de publication

Date de publication:
11 Mar 2024
Historique:
received: 13 10 2023
accepted: 19 02 2024
medline: 12 3 2024
pubmed: 12 3 2024
entrez: 12 3 2024
Statut: epublish

Résumé

Moloney murine leukemia virus (MLV) replication is suppressed in mouse embryonic stem cells (ESCs) by the Trim28-SETDB1 complex. The chromatin remodeler Smarcad1 interacts with Trim28 and was suggested to allow the deposition of the histone variant H3.3. However, the role of Trim28, H3.3, and Smarcad1 in MLV repression in ESCs still needs to be fully understood. In this study, we used MLV to explore the role of Smarcad1 in retroviral silencing in ESCs. We show that Smarcad1 is immediately recruited to the MLV provirus. Based on the repression dynamics of a GFP-reporter MLV, our findings suggest that Smarcad1 plays a critical role in the establishment and maintenance of MLV repression, as well as other Trim28-targeted genomic loci. Furthermore, Smarcad1 is important for stabilizing and strengthening Trim28 binding to the provirus over time, and its presence around the provirus is needed for proper deposition of H3.3 on the provirus. Surprisingly, the combined depletion of Smarcad1 and Trim28 results in enhanced MLV derepression, suggesting that these two proteins may also function independently to maintain repressive chromatin states. Overall, the results of this study provide evidence for the crucial role of Smarcad1 in the silencing of retroviral elements in embryonic stem cells. Further research is needed to fully understand how Smarcad1 and Trim28 cooperate and their implications for gene expression and genomic stability.

Sections du résumé

BACKGROUND BACKGROUND
Moloney murine leukemia virus (MLV) replication is suppressed in mouse embryonic stem cells (ESCs) by the Trim28-SETDB1 complex. The chromatin remodeler Smarcad1 interacts with Trim28 and was suggested to allow the deposition of the histone variant H3.3. However, the role of Trim28, H3.3, and Smarcad1 in MLV repression in ESCs still needs to be fully understood.
RESULTS RESULTS
In this study, we used MLV to explore the role of Smarcad1 in retroviral silencing in ESCs. We show that Smarcad1 is immediately recruited to the MLV provirus. Based on the repression dynamics of a GFP-reporter MLV, our findings suggest that Smarcad1 plays a critical role in the establishment and maintenance of MLV repression, as well as other Trim28-targeted genomic loci. Furthermore, Smarcad1 is important for stabilizing and strengthening Trim28 binding to the provirus over time, and its presence around the provirus is needed for proper deposition of H3.3 on the provirus. Surprisingly, the combined depletion of Smarcad1 and Trim28 results in enhanced MLV derepression, suggesting that these two proteins may also function independently to maintain repressive chromatin states.
CONCLUSIONS CONCLUSIONS
Overall, the results of this study provide evidence for the crucial role of Smarcad1 in the silencing of retroviral elements in embryonic stem cells. Further research is needed to fully understand how Smarcad1 and Trim28 cooperate and their implications for gene expression and genomic stability.

Identifiants

DOI: 10.1186/s13100-024-00314-z PMID: 38468276
pubmed: 38468276
doi: 10.1186/s13100-024-00314-z
pii: 10.1186/s13100-024-00314-z
doi:

Types de publication

Journal Article

Langues

eng

Pagination

4

Subventions

Organisme : Israel Science Foundation
ID : 761/17
Organisme : Israel Science Foundation
ID : 761/17
Organisme : Israel Science Foundation
ID : 761/17
Organisme : Israel Science Foundation
ID : 761/17

Informations de copyright

© 2024. The Author(s).

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Auteurs

Igor Bren (I)

Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.

Ayellet Tal (A)

Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.

Carmit Strauss (C)

Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.

Sharon Schlesinger (S)

Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel. sharon.shle@mail.huji.ac.il.

Classifications MeSH