HDAC3-/- Treg show abnormal mitochondria, impaired OCR and decreased electron transport chain gene expression.

Histone/protein Deacetylases

Histone/protein Deacetylases (HDACs) were first identified and studied as enzymes that remove acetyl groups from lysine residues within histone tails and thereby reduced chromatin accessibility by transcription factors and components of transcriptional complexes. However, HDACs are now known to regulate the acetylation of a large number of non-histone proteins, including Foxp3. Our ongoing HDAC studies, using genetic and pharmacologic approaches, center around analyzing the functions of individual HDACs in Foxp3+ Treg cells.

Selected Publications

Isoform-selective HDAC inhibitor therapy for transplantation: Are we ready for HDAC6? Hancock WW. Transplantation. 2016 Aug;100(8):1597-8.

FOXP3+ regulatory T cell development and function require histone/protein deacetylase 3. Wang L, Liu Y, Han R, Beier UH, Bhatti TR, Akimova T, Greene MI, Hiebert SW, Hancock WW. J Clin Invest. 2015 Mar 2;125(3):1111-23.
Free PMC Article

Histone deacetylases 6 and 9 and sirtuin-1 control Foxp3+ regulatory T cell function through shared and isoform-specific mechanisms. Beier UH, Wang L, Han R, Akimova T, Liu Y, Hancock WW. Sci Signal. 2012 Jun 19;5(229):ra45.
Free PMC Article

Histone deacetylase 6 and heat shock protein 90 control the functions of Foxp3(+) T-regulatory cells. de Zoeten EF, Wang L, Butler K, Beier UH, Akimova T, Sai H, Bradner JE, Mazitschek R, Kozikowski AP, Matthias P, Hancock WW. Mol Cell Biol. 2011 May;31(10):2066-78.
Free PMC Article

Histone/protein deacetylase inhibitors increase suppressive functions of human FOXP3+ Tregs. Akimova T, Ge G, Golovina T, Mikheeva T, Wang L, Riley JL, Hancock WW. Clin Immunol. 2010 Sep;136(3):348-63.
Free PMC Article

Inhibition of HDAC9 increases T regulatory cell function and prevents colitis in mice. de Zoeten EF, Wang L, Sai H, Dillmann WH, Hancock WW. Gastroenterology. 2010 Feb;138(2):583-94.
Free PMC Article

Immunomodulatory effects of deacetylase inhibitors: therapeutic targeting of FOXP3+ regulatory T cells. Wang L, de Zoeten EF, Greene MI, Hancock WW. Nat Rev Drug Discov. 2009 Dec;8(12):969-81.

Deacetylase inhibition promotes the generation and function of regulatory T cells. Tao R, de Zoeten EF, Ozkaynak E, Chen C, Wang L, Porrett PM, Li B, Turka LA, Olson EN, Greene MI, Wells AD, Hancock WW. Nat Med. 2007 Nov;13(11):1299-307.