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. 2009 May 28;284(30):20408–20417. doi: 10.1074/jbc.M109.016469

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© 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

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FIGURE 7. — A model for the regulation of SIRT1 activity at target gene promoters by NAMPT and NMNAT-1. SIRT1 binds to target gene promoters and regulates the acetylation status of transcription factors, histones, and other chromatin-associated proteins in an NAD⁺-dependent manner. Both NAMPT and NMNAT-1 localize to the nucleus and constitute an NAD⁺ recycling pathway. Nuclear NAD⁺ production by NAMPT and NMNAT-1 supports SIRT1 deacetylase activity. In addition, NMNAT-1 interacts with SIRT1 and is recruited to SIRT1 target gene promoters. Interactions between NMNAT-1 and SIRT1 on chromatin may underlie novel mechanisms for transcriptional regulation by SIRT1. TF, transcription factor. CoReg, coregulator.