AUTHOR=Krause Michael W. , Love Dona C. , Ghosh Salil K. , Wang Peng , Yun Sijung , Fukushige Tetsunari , Hanover John A. 

TITLE=Nutrient-Driven O-GlcNAcylation at Promoters Impacts Genome-Wide RNA Pol II Distribution

JOURNAL=Frontiers in Endocrinology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00521

DOI=10.3389/fendo.2018.00521

ISSN=1664-2392

ABSTRACT=<p>Nutrient-driven <italic>O</italic>-GlcNAcylation has been linked to epigenetic regulation of gene expression in metazoans. In <italic>C. elegans, O</italic>-GlcNAc marks the promoters of over 800 developmental, metabolic, and stress-related genes; these <italic>O</italic>-GlcNAc marked genes show a strong 5′, promoter-proximal bias in the distribution of RNA Polymerase II (Pol II). In response to starvation or feeding, the steady state distribution of <italic>O</italic>-GlcNAc at promoters remain nearly constant presumably due to dynamic cycling mediated by the transferase OGT-1 and the <italic>O</italic>-GlcNAcase OGA-1. However, in viable mutants lacking either of these enzymes of <italic>O</italic>-GlcNAc metabolism, the nutrient-responsive GlcNAcylation of promoters is dramatically altered. Blocked <italic>O</italic>-GlcNAc cycling leads to a striking nutrient-dependent accumulation of <italic>O</italic>-GlcNAc on RNA Pol II. <italic>O</italic>-GlcNAc cycling mutants also show an exaggerated, nutrient-responsive redistribution of promoter-proximal RNA Pol II isoforms and extensive transcriptional deregulation. Our findings suggest a complex interplay between the <italic>O</italic>-GlcNAc modification at promoters, the kinase-dependent “CTD-code,” and co-factors regulating RNA Pol II dynamics. Nutrient-responsive <italic>O</italic>-GlcNAc cycling may buffer the transcriptional apparatus from dramatic swings in nutrient availability by modulating promoter activity to meet metabolic and developmental needs.</p>