Complementary roles of gcn5 and pcaf in foxp3+ t-regulatory cells

Yujie Liu, Chunrong Bao, Liqing Wang, Rongxiang Han, Ulf H. Beier, Tatiana Akimova, Philip A. Cole, Sharon Y.R. Dent, Wayne W. Hancock

Research output: Contribution to journalArticle

Abstract

Functions of the GCN5-related N-acetyltransferase (GNAT) family of histone/protein acetyltransferases (HATs) in Foxp3+ T-regulatory (Treg) cells are unexplored, despite the general importance of these enzymes in cell biology. We now show that two prototypical GNAT family members, GCN5 (general control nonrepressed-protein 5, lysine acetyltransferase (KAT)2a) and p300/CBP-associated factor (p300/CBP-associated factor (PCAF), Kat2b) contribute to Treg functions through partially distinct and partially overlapping mechanisms. Deletion of Gcn5 or PCAF did not affect Treg development or suppressive function in vitro, but did affect inducible Treg (iTreg) development, and in vivo, abrogated Treg-dependent allograft survival. Contrasting effects were seen upon targeting of each HAT in all T cells; mice lacking GCN5 showed prolonged allograft survival, suggesting thisHAT might be a target for epigenetic therapy in allograft recipients, whereas transplants in mice lacking PCAF underwent acute allograft rejection. PCAF deletion also enhanced anti-tumor immunity in immunocompetent mice. Dual deletion of GCN5 and PCAF led to decreased Treg stability and numbers in peripheral lymphoid tissues, and mice succumbed to severe autoimmunity by 3–4 weeks of life. These data indicate that HATs of the GNAT family have contributions to Treg function that cannot be replaced by the functions of previously characterized Treg HATs (CBP, p300, and Tip60), and may be useful targets in immuno-oncology.

Original languageEnglish (US)
Article number554
JournalCancers
Volume11
Issue number4
DOIs
StatePublished - Apr 2019

Fingerprint

Histone Acetyltransferases
Acetyltransferases
Allografts
p300-CBP Transcription Factors
Proteins
Lymphoid Tissue
Regulatory T-Lymphocytes
Autoimmunity
Epigenomics
Cell Biology
p300-CBP-associated factor
Immunity
T-Lymphocytes
Enzymes
Neoplasms
Therapeutics

Keywords

  • Acetylation
  • Acetyltransferase
  • Anti-tumor immunity
  • Autoimmunity
  • Chromatin
  • Epigenetics
  • Transplantation
  • Treg cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Liu, Y., Bao, C., Wang, L., Han, R., Beier, U. H., Akimova, T., ... Hancock, W. W. (2019). Complementary roles of gcn5 and pcaf in foxp3+ t-regulatory cells. Cancers, 11(4), [554]. https://doi.org/10.3390/cancers11040554

Complementary roles of gcn5 and pcaf in foxp3+ t-regulatory cells. / Liu, Yujie; Bao, Chunrong; Wang, Liqing; Han, Rongxiang; Beier, Ulf H.; Akimova, Tatiana; Cole, Philip A.; Dent, Sharon Y.R.; Hancock, Wayne W.

In: Cancers, Vol. 11, No. 4, 554, 04.2019.

Research output: Contribution to journalArticle

Liu, Y, Bao, C, Wang, L, Han, R, Beier, UH, Akimova, T, Cole, PA, Dent, SYR & Hancock, WW 2019, 'Complementary roles of gcn5 and pcaf in foxp3+ t-regulatory cells', Cancers, vol. 11, no. 4, 554. https://doi.org/10.3390/cancers11040554
Liu Y, Bao C, Wang L, Han R, Beier UH, Akimova T et al. Complementary roles of gcn5 and pcaf in foxp3+ t-regulatory cells. Cancers. 2019 Apr;11(4). 554. https://doi.org/10.3390/cancers11040554
Liu, Yujie ; Bao, Chunrong ; Wang, Liqing ; Han, Rongxiang ; Beier, Ulf H. ; Akimova, Tatiana ; Cole, Philip A. ; Dent, Sharon Y.R. ; Hancock, Wayne W. / Complementary roles of gcn5 and pcaf in foxp3+ t-regulatory cells. In: Cancers. 2019 ; Vol. 11, No. 4.
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