Creation of p300-reconstituted ESCs. (A) p300 locus is shown in parental p300^−/−, master recipient, and reconstituted embryonic stem cells (ESCs). A neomycin cassette spanning exons 4 to 6 renders p300^−/− and master recipient ESC lines nullizygous for p300. A loxP/lox511 flanked targeting cassette containing a hygromycin resistance (hyg^R) gene replaces exon 2 and provides exchange site for CRE-mediated recombination with p300 donor plasmids, resulting in the production of p300-reconstituted ESCs. Dotted arrow indicates splicing occurs from endogenous exon 1 into the p300 cDNA cassette. (B) Panel of p300 cDNA constructs used to create reconstituted ESC lines. The specific amino acid (aa) deletion, mutation, or CBP replacement design is indicated for each construct.