The H3 histone modifications recognized by TRIM24, TRIM28, TRIM33, and TRIM66 have been the subject of a number of studies. The targets of the TRIM24 readers domains were identified by Tsai et al., reporting TRIM24 as a dual reader of unmodified H3K4 and H3K23Ac. Xi et al. have characterized TRIM33α, the full-length isoform of TRIM33. The PHD of TRIM33α binds to unmodified H3K4, and H3K9Me 3 through an interaction with W889. This residue is conserved in TRIM24, where binding to H3K9Me 3 has been reported but not quantified. The BRD of TRIM33α binds to H3K18Ac, which is an appropriate distance from H3K9 to be read simultaneously. A recent study by Chen et al. demonstrated that all peptides binding to the PHD of TRIM24, TRIM33, or TRIM66 require unmodified H3R2. The study by Xi et al. focused on the TRIM33α isoform, which contains a BRD with a 17-amino acid insertion on the BC loop, compared to the TRIM24 sequence. However, a second isoform of TRIM33 has been identified, TRIM33β, which is a splice variant that lacks the 17-amino acid insertion and is homologous to TRIM24. The histone H3 binding profile of TRIM33β has not previously been compared to TRIM33α, and the role of the extended BC loop in TRIM33α has not been explored. The X-ray crystal structures of TRIM33α show a non-canonical BRD, in which the conserved N1039 residue is located outside of the KAc-binding pocket, indicating that it cannot interact with KAc; 37 prior to this work the location of N1039 in TRIM33β was unknown.