The novel protein modification, O-linked N-acetylglucosamine (O-GlcNAc), plays ail important role in various aspects of cell regulation. Although most of nuclear transcription regulatory factors are modified by O-GlcNAc, O-GlcNAc effects oil transcription remain largely undefined yet. In this Study, we show that O-GlcNAc inhibits a physical interaction between Sp1 and Elf-1 transcription factors, and negatively regulates transcription of placenta and embryonic expression oncofetal protein gone (Pem). These findings Suggest that O-GlcNAc inhibits Sp1-mediated gene transcription possibly by interrupting Sp1 interaction with its cooperative factor. (C) 2009 Elsevier Inc. All rights reserved.