Biomedical subjects

Nicaulas A Sabourin

Publications and source records attributed to Nicaulas A Sabourin.

3 recordsLinked to original sources

PubMed2004

Capacitance-derived dielectric constants demonstrate differential preinitiation complexes in TBP-independent and TBP-dependent transcription.

The electronic properties of proteins and DNA may change dramatically upon complex formation, yet there are not many experimental methods which can be used to measure these properties. It has been previously shown that measuring the capacitance of a solution containing interacting DNA and protein species can yield information about changing dipole moments. The measured dielectric constant relates directly to the dipole moment of the complexes in solution. Here, we apply this method to partial transcription initiation complexes in order to investigate the changing electronic properties in the transcriptional preinitiation complex. These experiments are the first reported observations relating to the overall dipole moment and its changes in preinitiation complex formation. Comparing results from TBP-independent and TBP-dependent transcriptional systems shows a divergence in the electronic properties of built-up transcription complexes, suggesting that they initiate transcription by significantly different electronic and structural pathways.

DNA-Binding Proteins↗

PubMed2003

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.

Acetylglucosamine↗

PubMed2003

YY1-DNA interaction results in a significant change of electronic context as measured by capacitance.

The detailed mechanism behind the processes of DNA-dependent RNA transcription initiation is largely unknown. When transcription initiation factors bind DNA, a significant change in the electrostatic state of the complex can result. Using electrical capacitance measurements of solutions of the YY1 zinc finger transcription initiation factor and the adeno-associated viral P5 promoter DNA, we observed a specific dielectric change when a protein-DNA complex was formed. We propose that complexation results in electrostatic changes that may trigger the markedly different electrical behavior, and offer a possible explanation for our results.

Adenoviridae↗