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[Preprint]. 2024 Feb 1:2023.12.28.573526. [Version 3] doi: 10.1101/2023.12.28.573526

Figure 7: Interaction of Two Human Silencing Hub (HuSH) Complexes in Controlling LINE-1 Element Silencing.

Figure 7:

The model proposed for the silencing of LINE-1 elements by the HuSH complex is depicted in this figure. In K-562 cells under normal conditions, TASOR functions as a central hub, orchestrating the interaction between MPP8 and PPHLN1, collectively forming the HuSH complex. This complex is further associated with additional factors that likely contribute to the regulation of its recruitment to chromatin, thereby influencing the subsequent silencing of LINE-1 elements. In K-562 cells, where LINE-1 expression is typically low, the abundance of the HuSH complex plays a crucial role. However, perturbations in the balance of its components can lead to alterations in LINE-1 expression levels. Specifically, when there is an increase in HuSH2, either through the reduction of TASOR or the elevation of TASOR2, the balance of HuSH complexes begins to change. This results in the titration of MPP8 and PPHLN1, leading to a decrease in the overall abundance of HuSH. Consequently, this derepression of LINE-1 elements occurs, indicating a dynamic interplay within the HuSH complex that directly influences the regulation of LINE-1 elements in K-562 cells.