Gene expression profiles of CBPWTp53-floxed, CBPAAp53-floxed,CBPWTp53ΔIEC and CBPAAp53ΔIEC intestinal cyrpts

CREB-binding protein (CBP) is a coactivator modulating DNA accessibility for transcription factors.CBP phosphorylation at Ser1382/1386 enhanced NF- B- while suppressed p53-mediated gene expression to promote cell growth, suggesting that post-translational modification of CBP regulates cell fate. Here we report that CBP knock-in mice (CBPAA), in which Ser1383/1387 are replaced with alanines, develop a phenotype resembling ulcerative colitis (UC) driven by non-hematopoietic cells. These mice exhibit reduced organoid formation, intestinal epithelial cell (IEC) proliferation, accompanied by increased CBP/p53 binding. All findings are reversed in CBPAA mice with IEC-specific p53 deletion (CBPAAp53ΔIEC) mice. To investigate how impaired CBP phosphorylation results in dampened IEC stemness, RNA-seq was performed to profile the transcriptome of colonic crypt.