Editing Histone octamer (section)

==Clinical relevance==

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.<ref name="Translating the histone code">{{cite journal|last=Jenuwein|first=T|author2=Allis, CD|title=Translating the histone code|journal=Science|date=Aug 10, 2001|volume=293|issue=5532|pages=1074–80|pmid=11498575|doi=10.1126/science.1063127|citeseerx=10.1.1.453.900|s2cid=1883924}}</ref>   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-CBP coactivator family|p300]] and cAMP response element-binding protein ([[Calcium-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.<ref name="Overlapping but distinct patterns of histone acetylation by the human coactivators p300 and PCAF within nucleosomal substrates.">{{cite journal|last=Schiltz|first=RL|author2=Mizzen, CA |author3=Vassilev, A |author4=Cook, RG |author5=Allis, CD |author6= Nakatani, Y |title=Overlapping but distinct patterns of histone acetylation by the human coactivators p300 and PCAF within nucleosomal substrates.|journal=The Journal of Biological Chemistry|date=Jan 15, 1999|volume=274|issue=3|pages=1189–92|pmid=9880483|doi=10.1074/jbc.274.3.1189|doi-access=free}}</ref>  Lysine 18 and Lysine 27 on H3 were the only histone acetylation sites reduced upon CBP and p300 depletion in mouse embryonic fibroblasts.<ref name="Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation.">{{cite journal|last=Jin|first=Q|author2=Yu, LR |author3=Wang, L |author4=Zhang, Z |author5=Kasper, LH |author6=Lee, JE |author7=Wang, C |author8=Brindle, PK |author9=Dent, SY |author10= Ge, K |title=Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation.|journal=The EMBO Journal|date=Jan 19, 2011|volume=30|issue=2|pages=249–62|pmid=21131905|doi=10.1038/emboj.2010.318 |pmc=3025463}}</ref>  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+/−.<ref name="Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300.">{{cite journal|last=Yao|first=TP|author2=Oh, SP |author3=Fuchs, M |author4=Zhou, ND |author5=Ch'ng, LE |author6=Newsome, D |author7=Bronson, RT |author8=Li, E |author9=Livingston, DM |author10= Eckner, R |title=Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300.|journal=Cell|date=May 1, 1998|volume=93|issue=3|pages=361–72|pmid=9590171|doi=10.1016/S0092-8674(00)81165-4|s2cid=620460|doi-access=free}}</ref>  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.