YY1 is regulated by O-linked N-acetylglucosaminylation (O-glcNAcylation).
YY1 is a zinc finger DNA-binding transcription factor that influences expression of a wide variety of cellular and viral genes. YY1 is essential for the development of mammalian embryos. It regulates the expression of genes with important functions in DNA replication, protein synthesis, and cellular response to external stimuli during cell growth and differentiation. How YY1 accomplishes such a variety of functions is unknown. Here, we show that a subset of the nuclear YY1 appears to be O-GlcNAcylated regardless of the differentiation status of the cells. We found that glucose strongly stimulates O-linked N-acetylglucosaminylation (O-GlcNAcylation) on YY1. Glycosylated YY1 no longer binds the retinoblastoma protein (Rb). Upon dissociation from Rb, the glycosylated YY1 is free to bind DNA. The ability of the O-glycosylation on YY1 to disrupt the complex with Rb leads us to propose that O-glycosylation might have a profound effect on cell cycle transitions that regulate the YY1-Rb heterodimerization and promote the activity of YY1. Our observations provide strong evidence that YY1-regulated transcription is very likely connected to the pathway of glucose metabolism that culminates in the O-GlcNAcylation on YY1, changing its function in transcription.
Hiromura
Makoto
M
Beth Israel Deaconess Medical Center, Department of Medicine, Endocrinology, Harvard Medical School, Boston, Massachussetts 02215, USA.
Choi
Chu H
CH
Sabourin
Nicaulas A
NA
Jones
Heath
H
Bachvarov
Dimcho
D
Usheva
Anny
A
D000117:Acetylglucosamine / Q000378:metabolism*; D000581:Amidohydrolases / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000378:metabolism; D015153:Blotting, Western; D002241:Carbohydrates / Q000737:chemistry; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D005700:Galactosyltransferases / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007313:Insecta; D009130:Muscle, Smooth / Q000166:cytology; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D050986:YY1 Transcription Factor
D002241:Carbohydrates; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D005700:Galactosyltransferases; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D005947:Glucose; D000117:Acetylglucosamine