Numerous reports show a link between age-related diseases, birth defects, and several types of cancer with disruption of certain histone post translational modifications.  Studies have identified that N- and C-terminal tails are main targets for acetylation, methylation, ubiquitination and phosphorylation.   New evidence is pointing to several modifications within the histone core.  Research is turning towards deciphering the role of these histone core modifications at the histone-DNA interface in the chromatin.  p300 and cAMP response element-binding protein (CBP) possess histone acetyltransferase activity.  p300 and CBP are the most promiscuous histone acetyltransferase enzymes acetylating all four core histones on multiple residues.  Lysine 18 and Lysine 27 on H3 were the only histone acetylation sites reduced upon CBP and p300 depletion in mouse embryonic fibroblasts.  Also,  CBP and p300 knockout mice have an open neural tube defect and therefore die before birth.  p300−/−  embryos exhibit defective development of the heart.  CBP+/− mice display growth retardation, craniofacial abnormalities, hematological malignancies, which are not observed in mice with p300+/−.  Mutations of both p300 have been reported in human tumors such as colorectal, gastric, breast, ovarian, lung, and pancreatic carcinomas.  Also, activation or localization of two histone acetyltransferases can be oncogenic.