Figure 7.

Model of the role of ING1 in regulating Pol I transcription. rDNA transcription is tightly regulated by epigenetic mechanisms and growth factor/kinase signaling, partly through mTOR that integrates many growth signals. The interaction of Pol I complex subunits with the transcription machinery including UBF1 is required for the formation of enhanceosomes and promoter melting. Histone modifying enzymes acetylate proteins within the rDNA repeats to make them more accessible to the Pol I transcriptional machinery. ING1 reduces mTOR localization to nucleoli and helps recruit HDAC1 to the NoRC complex and to UBF for deacetylation and transcriptional repression. Loss of ING1 also increased H3 acetylation and increased the number of active rDNA units available for transcription. This study suggests that ING1 facilitates HDAC1 activity and antagonizes mTOR function in the nucleolus, and is required for maintaining a portion of the rDNA repeats in a silenced state in normally replicating cells and during differentiation of monocytes.