SIRT1, member of the sirtuins family, is an NAD-dependent deacetylase, playing an essential role in controlling gene expression. In addition to modifying histones, SIRT1 can affect the activity of several transcription factors and their target genes. A fundamental question is to understand the molecular mechanisms by which SIRT1 controls the expression of genesinvolved in cell proliferation and energy metabolism. To identify protein partners of SIRT1, we used the method of TAP-TAG purification from a soluble nuclear fraction and a chromatin anchored fraction of Mef cells stably expressing ectopic copy of SIRT1 (SIRT1-e). We were able to identify a SIRT1 complex associated with both cell proliferation factor Ki67, and TFIIIC,subunit required for assembly of the RNA polymerase III pre-initiation complex. By deleting Sirt1, and by specifically inhibiting Ki67 expression, we showed that the RNA Polymerase III transcription machinery and cell proliferation were strongly affected. All of my results clearly shows that SIRT1, Ki67, and TFIIIC are within a same protein complex, SIRT1 and Ki67, acting in coordination to regulate the expression level of SINES and LINES, transcribed from RNA polymerase III transcription machinery.
Epigenetic regulation of polymerase III RNA transcription machinery by histone deacetylase SIRT1