The lab has made significant progress in our understanding of pol IIgamma functions. pol IIgamma does indeed have a novel role in transcription initiation and we are continuing experiments to define this role more precisely. Nevertheless, our hypothesis seems to be correct. Furthermore, we have identified a cycle of GlcNAc addition and removal that is occurring on pol II while it resides on the promoter (hereafter referred to as the G-cycle). Any disruptions of this cycle lead to complete abrogation of transcription. Data thus far indicates this cycle occurs during assembly and recruitment of factors to the promoter. As expected, the pol II CTD is a legitimate substrate for both O-GlcNAc transferase (OGT) and O-GlcNAc aminidase (OGA), the enzymes required for the addition and removal of GlcNAc to and from protein substrates, respectively. We have also gained some insight into the regulation of these enzymes on the promoter, specifically the OGA. We have preliminary data that OGA activity can be regulated by a general transcription factor, TFIIF, which is necessary for pol II recruitment to the promoter and which also physically and functionally interacts with pol II. Finally, additional data suggests an intermediary which physically links pol II and OGA. We are further pursuing this protein to address any functional involvement in G-cycle regulation.

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National Cancer Institute (NCI)
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Lewis, Brian A; Burlingame, Alma L; Myers, Samuel A (2016) Human RNA Polymerase II Promoter Recruitment in Vitro Is Regulated by O-Linked N-Acetylglucosaminyltransferase (OGT). J Biol Chem 291:14056-61
Lewis, Brian A; Hanover, John A (2014) O-GlcNAc and the epigenetic regulation of gene expression. J Biol Chem 289:34440-8
Ranuncolo, Stella M; Ghosh, Salil; Hanover, John A et al. (2012) Evidence of the involvement of O-GlcNAc-modified human RNA polymerase II CTD in transcription in vitro and in vivo. J Biol Chem 287:23549-61