In pluripotent mouse embryonic stem cells (ESCs), SetDB1, which targets up to twenty thousand genomic loci, plays an essential role in regulating various cellular processes, including maintenance of the embryonic stem cell state, differentiation and metabolism. SetDB1 is best known as a chromatin modifier catalyzing H3K9me3. However, recent studies show that SetDB1 can mediate H3K27me3-deposition by PRC2, CTCF-binding, recruit DNA methyltransferases, and potentially regulate additional chromatin processes. To gain further insights, we profiled the chromatin-bound protein landscapes of WT mouse ESCs, as well as SetDB1-deficient mouse ESCs at different time points after inducing Setdb1 KO, using Chromatin Enrichment for Proteomics (ChEP + LC-MS/MS).