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Usheva Lab

Our Major Research Interests

  • The major purpose of our research is to establish the mechanisms that operate in the expression process of genetic information in biological systems. We search for links between control of gene expression and metabolic status. We search for the potential role of protein acetylation and glycosylation in the modulation of gene expression patterns both acutely - in terms of food restriction - and chronically in diabetes and aging. We are particularly interested in the regulation of gene expression at the level of DNA transcription. We approach it at four different levels - at the electronic and thermodynamic levels, at the molecular level, and at the cellular and mammalian tissue levels. 

Current Research

  • Recently we illustrated coherent localized dynamics of DNA that may prove to be a major determinant of DNA functions such as the initiation of gene transcription. We demonstrated that structurally specific coherent thermal fluctuations identify locations in the DNA sequences where the RNA polymerases initiate transcription. Further, we discovered indications that the thermal fluctuations help in recruiting other protein complexes participating in the transcriptional process by DNA double strand distortion at specific locations. Our observations suggest that DNA participates in directing its transcription through structurally specific dynamics.
  • We investigate how proteins regulate gene transcription at the level of protein-DNA and protein-protein interactions. Post-translational modifications of transcription factors such as acetylation play an important regulatory function by acting as switches of activity. Recently we discovered a new autoenzymatic acetylation activity in the general transcription factor IIB (TFIIB), a protein required for eukaryotic polymerase II transcription. Our finding suggests a new view of the role and importance of acetylation in transcription - the potential self-regulation of core promoter activity and its dependence on acetyl-TFIIB. As acetyl-CoA is an important cofactor in this reaction, this finding demonstrates that basic transcription may be linked to fatty-acid synthesis and cellular respiration. The implications of such connections would be far-reaching in cellular biology. We propose that the acetylation of TFIIB is capable of regulating transcription in response to fasting and aging. This would establish a novel role for acetyl-CoA as a metabolic regulator of transcription.
  • We are investigating the functionality of transcription factor YY1, which regulates basal transcription of several genes that are directly involved in the vascular response to vascular injury and atherosclerosis development. Recently we reported that YY1 is O-glycosylated. O-GlcNAcylation is a protein modification on serine or threonine residue with a monosaccharide, N-acetylglucosamine, in an O-glycosidic linkage. We are particularly interested in determining whether O-GlcNAcylation of YY1 regulates YY1-Rb/Notch interactions and downstream gene transcription leading to triggering of vascular response to injury and atherosclerosis.

    For a complete listing of Dr. Usheva's publications, click here  or click the "Publications" link on the sidebar to the left .

Contact Information

Usheva Lab
Beth Israel Deaconess Medical Center
Masco 4
330 Brookline Avenue
Boston, MA 02215