Transcription intermediary factor 1γ decreases protein expression of the transcriptional cofactor, LIM-domain-binding 1

LIM-domain-binding 1 (LDB1) is a cofactor that participates in formation of regulatory complexes involving transcription factors containing LIM domains as well as other factors. We have examined the ability of transcriptional intermediary factor 1γ (TIF1γ) to decrease LDB1 expression. An expression vector for TIF1γ was found to decrease expression of LDB1. A mutation which disrupts the ubiquitin ligase activity of TIF1γ was found to block the ability of TIF1γ to decrease LDB1 expression. Proteasome inhibitors were also able to block TIF1γ effects on LDB1. Immunoprecipitation studies provided evidence that LDB1 interacts with TIF1γ in intact cells. Knockdown of TIF1γ in zebrafish embryos led to increased expression of LDB1 providing evidence for a physiological role of TIF1γ in regulating LDB1 expression. Reporter gene assays demonstrated that TIF1γ can alter the activity of LIM-homeodomain transcription factor-responsive promoters. These studies are consistent with a model in which TIF1γ acts to ubiquitinate LDB1 leading to degradation of LDB1 and changes in transcription of LDB1-dependent promoters.