To identify oligomerization dependent interactors of C-terminal binding protein 2 (CTBP2), we stably expressed CTBP2 wild type or a monomeric mutant (CTBP2 mono: CTBP2 C140Y, N144R, R147E, L156W) in Ctbp1-/-, Ctbp2-/- J774.1 cells and profiled their genome-wide interactome in LPS conditions after 3 h of stimulation. Differential profiling of CTBP2’s wild type and monomeric interactome shows oligomer-specific interactions with multiple repressors including KDM1A and the NuRD complex. Conversely, monomers retain the ability to interact with AP-1 and RNA polymerase II.