been implicated in influencing nutrient sensing and metabolism. Further study may also help in identifying the principal mechanisms through which OGT and OGA antagonists may drive therapeutic benefits. Thinking more broadly, the incredible increases in cost efficient sequencing coupled with proliferation of metabolic feeding strategies to label different protein and nucleic acid modifications point to general utility for metabolic labeling and time course-based ChIP-seq strategies in line with the experiments we have described. Researchers from various fields can exploit the methods we describe here to understand dynamic changes to diverse protein modifications found within the genome and thereby help define their roles in regulating the physiology of cells and organisms.In vivo genome wide dynamics of O-GlcNAcylated chromatin-associated proteins brainDavid J. Vocadloare O-GlcNAcylated in response to this stress were identified and show enhanced binding to the genome. Among these, nuclear respiratory factor 1 (NRF1) appears to be an important O-GlcNAc dependent regulator of cellular homeostasis. Collectively, these data support OGA acting in an important manner to regulate the function of chromatin-bound proteins and downstream gene expression. The definition of O-GlcNAc modified genomic loci will enable more widely exploring the roles of this modification in the regulation of gene expression, as well as permitting the analysis of the identity and roles of O-GlcNAcylated proteins at OGA-resistant loci. We foresee great value in this approach being applied to examine the effects of altered nutrient availability, where O-GlcNAc has References 1) Hart GW, Housley MP, Slawson C. Cycling of O-Linked beta-N-acetylglucosamine on nucleocytoplasmic proteins. Nature (446): 1017−1022, 2007 2) Kassis JA, Brown JL. Polycomb group response elements in Drosophila and vertebrates. Adv. Genet. (81): 83–118, 2013 3) Gambetta MC, Oktaba K, Muller J. Essential role of the glycosyltransferase Sxc/Ogt in polycomb repression. Science (325) 93-96, 2009. 4) Sinclair DAR, Syrzycka M, Macauley MS, Rastgardani T, Komljenovic I, Vocadlo DJ, Brock HW, Honda BM. Drosophila O-GlcNAc transferase (OGT) 5) Kelly WG, Hart GW. Glycosylation of chromosomal proteins: localization of O-linked N-acetylglucosamine in Drosophila chromatin. Cell (57): 243– 6) Gambetta MC, Müller J. O-GlcNAcylation prevents aggregation of the polycomb group repressor polyhomeotic. Dev. Cell (31): 629-639, 2014 7) Liu TW, Myschyshyn M, Sinclair DA, Cecioni S, Beja K, Honda BM, Morin RD, Vocadlo DJ. Genome-wide chemical mapping of O-GlcNAcylated 8) A chemical genetic method for monitoring genome-wide dynamics of O-GlcNAc turnover on chromatin-associated proteins. Liu TW, Myschyshyn M, 9) Myschyshyn, M.; Farren-Dai, M.; Chuang, T.-J.; Vocadlo, D. Software for rapid time dependent ChIP-sequencing analysis (TDCA). BMC Bioinf. (18): is encoded by the Polycomb Group (PcG) gene, super sex combs. Proc. Natl. Acad. Sci., USA (106): 13427–13432, 2009251, 1989proteins in Drosophila melanogaster. Nat. Chem. Biol. (13): 161-167, 2017Sinclair DA, Vocadlo DJ. ACS Cent. Sci. (5): 663-670, 2019521, 201710) Liu Y, Chen Q, Zhang N, et al. Proteomic profiling and genome-wide mapping of O-GlcNAc chromatin-associated proteins reveal an O-GlcNAc-regulated genotoxic stress response. Nat Commun. (11): 5898, 202070
元のページ ../index.html#70