Editors' ChoiceGlycosylation

Sugar-Coating Gene Expression

See allHide authors and affiliations

Science's STKE  23 Jul 2002:
Vol. 2002, Issue 142, pp. tw261-TW261
DOI: 10.1126/stke.2002.142.tw261

Two groups report glycosylation of transcriptional regulators. Yang et al. provide evidence that the enzyme that catalyzes the addition of O-linked N-acetylglucosamine (O-GlcNAc) is recruited to promoters that are repressed. O-GlcNAc transferase (OGT) interacted with mammalian Sin3 (mSin3), a scaffold for corepressor complex formation. Using reporter genes, Yang et al. found that targeting OGT to a promoter inhibited transcription. OGT with and without the catalytic domain retained the ability to inhibit transcription, suggesting that there may be two mechanisms by which OGT contributes to transcriptional repression. OGT, mSin3, and the histone deacetylase HDAC1 coprecipitated, suggesting an interaction between OGT and the corepressor complex in vivo. In the presence of an inhibitor of HDAC activity, mSin3 interaction with OGT appeared to contribute to mSin3 transcriptional repression, because transcriptional activity was higher if the interaction domain between mSin3 and OGT was removed. Finally, mSin3 and HDAC1 are modified by the addition of O-GlcNAc. In breast cancer cells, depletion of estrogen caused increased association of O-GlcNAc-modified proteins with estrogen-responsive promoters.

Kane et al. provide evidence that the transcription factor NFIC is modified by N-glycosylation during mammary gland involution in mice. As seen from electrophoretic mobility shift assays, NFIC that is bound to DNA from lactating mammary gland migrated with a smaller apparent size (49 kD), whereas NFIC that is associated with DNA during early stages of involution appeared to be a larger protein (74 kD). The 74-kD NFIC bound conconavalin A, a lectin that recognizes α-mannose in the core of N-linked glycans; whereas the 49-kD form did not. The apparent size of the 74-kD NFIC associated with involution was decreased following treatment with a specific N-glycanase. Furthermore, the larger form of the protein was not formed in mammary glands or transfected cells in which N-glycosylation was inhibited by tunicamycin. Thus, N-glycosylation appears to be the posttranslational modification responsible for the change in size of NFIC. What remains unknown is how this posttranslational modification might affect the transcriptional activity of NFIC.

X. Yang, F. Zhang, J. E. Kudlow, Recruitment of O-GlcNAc transferase to promoters by corepressor mSin3A: Coupling protein O-GlcNAcylation to transcriptional repression. Cell 110, 69-80 (2002). [Online Journal]

R. Kane, J. Murtagh, D. Finaly, A. Marti, R. Jaggi, D. Blatchford, C. Wilde, F. Martin, Transcription factor NFIC undergoes N-glycosylation during early mammary gland involution. J. Biol. Chem. 277, 25893-25903 (2002). [Abstract] [Full Text]

Stay Connected to Science Signaling