Repression of LXRα by a novel member of additional sex comb-like family, ASXL3

Among the members of the additional sex comb-like (ASXL) family, ASXL3 remains unexplored. Here, we showed that ASXL3 interacts with HP1α and LSD1, leading to transcriptional repression. We determined that ASXL3 depletion augments the ligand-induced transcriptional activities of LXRα and TRβ, which were repressed by ASXL3 overexpression. The ligand-dependent interactions of ASXL3 with LXRα and TRβ were demonstrated by the GST pull-down and immunoprecipitation analyses. We confirmed that ASXL3 suppresses the expression of LXRα target genes through its recruitment to the LXR-response elements. Finally, we observed that lipid accumulation in Hep3B cells is downregulated upon ASXL3 overexpression but upregulated upon ASXL3 depletion. Overall, our data suggest that ASXL3 is another corepressor of LXRα, promoting to the regulation of lipid homeostasis.