TOR (target of rapamycin) has been previously implicated in transcriptional stimulation of the ribosomal protein (RP) genes via enhanced recruitment of NuA4 (nucleosome acetyltransferase of H4) to the promoters. However, it is not clearly understood how TOR enhances NuA4 recruitment to the promoters of the RP genes. Here we show that TOR facilitates the recruitment of the 19S proteasome subcomplex to the activator to enhance the targeting of NuA4 to the promoters of the RP genes. NuA4, in turn, promotes the recruitment of TFIID (transcription factor IID, composed of TATA box-binding protein [TBP] and a set of TBP-associated factors [TAFs]) and RNA polymerase II to the promoters of the RP genes to enhance transcriptional initiation. Therefore, our results demonstrate that TOR facilitates the recruitment of the 19S proteasome subcomplex to the promoters of the RP genes to promote the targeting of NuA4 for enhanced preinitiation complex (PIC) formation and consequently transcriptional initiation, hence illuminating TOR regulation of RP gene activation. Further, our results reveal that TOR differentially regulates PIC formation (and hence transcription) at the non-RP genes, thus demonstrating a complex regulation of gene activation by TOR.

• PMID: 29712756
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Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't

Authors

Uprety B, Kaja A, Bhaumik SR

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