It can coordinate with the PRC2 complex to promote H3K27 trimethylation,22 with SUV39H1/HP1/DNMT3A to facilitate H3K9 trimethylation and DNA methylation,41 or with the DIN3A-HDAC complex to deacetylate H3 and H4.23 KLF4 expression in cancer and stem cells has been shown to be modulated by epigenetic control, such as DNA methylation and histone methylation.42,43 Here, we demonstrate that CRL4B binds to the promoters of Klf4 and Cebpd and epigenetically represses Klf4 and Cebpd transcription through coordination with EZH2 and HDAC1/3. This evidence concerns the gene KLF4 and cancer.