Here we report an analysis of the histone H3 peptide binding profile of TRIM24, TRIM33α, and TRIM33β. We show that both TRIM33α and TRIM33β bind preferentially to H3 1-27 K9Me 3 K18Ac. Surprisingly, we found that TRIM33α and TRIM33β have similar binding affinities for H3 1- 27 K18Ac, despite the non-canonical BRD of TRIM33α. We also show that the PHD and BRD of these proteins contribute equally to the affinity for the dual modified H3 1-27 K9Me 3 K18Ac peptide, and that this contribution is additive. We have employed this information to develop an AlphaScreen assay for the tandem PHD-BRD cassettes of TRIM24, TRIM33α, and TRIM33β.