Figure 1.

p300 hypomorphic mutant (plt6/6) mouse intestinal defects phenocopy Myb mutant mice. (a) Like Myb hypomorphs, plt6/6 mutant mice have shorter crypts than WT mice (P=0.03). (b) This reduced crypt length corresponds to reduced proliferation, as determined by PCNA staining at crypts positions from the base (P<0.05–0.01). (c) Expression of ISC gene Myb is significantly reduced in colonic crypts isolated from plt6/6 mutants compared with WT as is Myb target and ISC gene, lgr5, P<0.01. (d) p300 and Myb can be viewed as being part of a larger complex of interacting TFs, including β-catenin, and most particularly, closely related CREB family members (CREB, CREM and ATF1) and more distantly related, ATF2. Linear protein lengths are shown in amino acid (AA) residues, and key interaction and function domains (DNA-binding domain (BD), transactivation domain (T/A), negative regulation domain (NRD) with leucine zipper-like domain (LZ), C=conserved homology domains (Ch), kinase interaction domain (KIX) and key conserved phosphorylation site (P). Means±S.E.M. one-tailed t-test