Correlation Engine 2.0
Clear Search sequence regions

  • bclaf1 (10)
  • CD28 (3)
  • E1A (2)
  • Ep300 protein (1)
  • factor (3)
  • GCN5 (1)
  • humans (1)
  • IL 2 (1)
  • Interleukin 2 (2)
  • lymphocyte (1)
  • mice (1)
  • NF κB (1)
  • p300 (7)
  • protein t (1)
  • regulates (1)
  • repressor proteins (2)
  • Sirt1 protein (2)
  • Sirtuin 1 (2)
  • t cell receptor (1)
  • t lymphocytes (11)
  • Sizes of these terms reflect their relevance to your search.

    The NAD-dependent histone deacetylase Sirt1 is a negative regulator of T cell activation. Here we report that Sirt1 inhibits T cell activation by suppressing the transcription of Bcl2-associated factor 1 (Bclaf1), a protein required for T cell activation. Sirt1-null T cells have increased acetylation of the histone 3 lysine 56 residue (H3K56) at the bclaf1 promoter, as well as increasing Bclaf1 transcription. Sirt1 binds to bclaf1 promoter upon T cell receptor (TCR)/CD28 stimulation by forming a complex with histone acetyltransferase p300 and NF-κB transcription factor Rel-A. The recruitment of Sirt1, but not p300, requires Rel-A because blocking Rel-A nuclear translocation in T cells and siRNA-mediated knockdown of Rel-A can inhibit Sirt1 binding to bclaf1 promoter. Although knockdown of either p300 or GCN5 partially suppressed global H3K56 acetylation, only p300 knockdown specifically attenuated H3K56 acetylation at the bclaf1 promoter. Lastly, knockdown of Bclaf1 suppresses the hyperactivation observed in Sirt1(-/-) T cells, indicated by less IL-2 production in CD4(+) T cells and reduced proliferation. Therefore, Sirt1 negatively regulates T cell activation via H3K56 deacetylation at the promoter region to inhibit transcription of Bclaf1.


    Sinyi Kong, Seung-Jae Kim, Barry Sandal, Sang-Myeong Lee, Beixue Gao, Donna D Zhang, Deyu Fang. The type III histone deacetylase Sirt1 protein suppresses p300-mediated histone H3 lysine 56 acetylation at Bclaf1 promoter to inhibit T cell activation. The Journal of biological chemistry. 2011 May 13;286(19):16967-75

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 21454709

    View Full Text