Genome-wide chemical mapping of O-GlcNAcylated proteins in Drosophila melanogaster.

Abstract:

:N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. Using Drosophila, we identify new O-GlcNAcylated PcG proteins and develop an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing. We find that O-GlcNAc is distributed to specific genomic loci both in cells and in vivo. Many of these loci overlap with PREs, but O-GlcNAc is also present at other loci lacking PREs. Loss of OGT leads to altered gene expression not only at loci containing PREs but also at loci lacking PREs, including several heterochromatic genes. These data suggest that O-GlcNAc acts through multiple mechanisms to regulate gene expression in Drosophila.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Liu TW,Myschyshyn M,Sinclair DA,Cecioni S,Beja K,Honda BM,Morin RD,Vocadlo DJ

doi

10.1038/nchembio.2247

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

161-167

issue

2

eissn

1552-4450

issn

1552-4469

pii

nchembio.2247

journal_volume

13

pub_type

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