Acting in a complementary manner to HDACs, Histone/protein acetyltransferases (HATs) catalyze acetylation of lysine residues within histone tails and also many non-histone proteins, including Foxp3. Our studies of the various HATs, using genetic and pharmacologic approaches, are focused on the functions of individual HATs within Treg cells. The development of HAT inhibitors is far less advanced than that of HDAC inhibitors, and are ongoing studies include in vivo studies with tumor models in syngeneic mice, as well as efforts to produce new and specific small molecule inhibitors.
Ubiquitin-specific protease-7 inhibition impairs Tip60-dependent Foxp3+ T-regulatory cell function and promotes antitumor immunity. Wang L, Kumar S, Dahiya S, Wang F, Wu J, Newick K, Han R, Samanta A, Beier UH, Akimova T, Bhatti TR, Nicholson B, Kodrasov MP, Agarwal S, Sterner DE, Gu W, Weinstock J, Butt TR, Albelda SM, Hancock WW. EBioMedicine. 2016 Nov;13:99-112. Free PMC Article
Two histone/protein acetyltransferases, CBP and p300, are indispensable for Foxp3+ T-regulatory cell development and function. Liu Y, Wang L, Han R, Beier UH, Akimova T, Bhatti T, Xiao H, Cole PA, Brindle PK, Hancock WW. Mol Cell Biol. 2014 Nov;34(21):3993-4007. Free PMC Article
Dynamic interactions between TIP60 and p300 regulate FOXP3 function through a structural switch defined by a single lysine on TIP60. Xiao Y, Nagai Y, Deng G, Ohtani T, Zhu Z, Zhou Z, Zhang H, Ji MQ, Lough JW, Samanta A, Hancock WW, Greene MI. Cell Rep. 2014 Jun 12;7(5):1471-80. Free PMC Article
Inhibition of p300 impairs Foxp3⁺ T regulatory cell function and promotes antitumor immunity. Liu Y, Wang L, Predina J, Han R, Beier UH, Wang LC, Kapoor V, Bhatti TR, Akimova T, Singhal S, Brindle PK, Cole PA, Albelda SM, Hancock WW. Nat Med. 2013 Sep;19(9):1173-7. Free PMC Article