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bioRxiv · 10.1101/2023.05.18.541392

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

Bren, I.·Strauss, C.·Schlesinger, S.
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Abstract

BackgroundMoloney 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. ResultsIn 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. ConclusionsOverall, 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. Take homeO_LIDepletion of Smarcad1 impairs retroviral repression. C_LIO_LISmarcad1 is necessary for proper recruitment of Trim28 and H3.3 deposition. C_LIO_LIDepleting Smarcad1 and Trim28 results in enhanced derepression of the MLV provirus. C_LI

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Bren, I., Strauss, C., Schlesinger, S.. 2023-05-19. The role of Smarcad1 in retroviral repression in mouse embryonic stem cells. https://doi.org/10.1101/2023.05.18.541392

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