TLE1 binds to the Runt domain and the C terminus of AML1 (RUNX1), but not to CBFB, mainly through the SP domain but also through the WD-40 domain of TLE1. Binding of TLE1 to the C terminus of RUNX1 inhibits RUNX1-induced transactivation of the CSF1 receptor (CSF1R). Northern blot analysis detected TLE1 transcripts of 4.4 and 2.6 kb. Expression was highest in skeletal muscle and liver, moderate in placenta, heart, kidney, and spleen, and weak in all other tissues examined, including brain.Mutation analysis showed that both the AF1 and AF2 domains of Esrrg2 were required for TLE1-dependent transactivation. The WD40 domain of TLE1 was required for interaction with Esrrg2, and the GP and Q domains of TLE1 were important for Esrrg2 coactivation.