Daniel Reines

BIOGRAPHY

ACADEMIC POSITION:
• Professor of Biochemistry, Emory University School of Medicine

EDUCATION:
PhD Albert Einstein College of Medicine, 1985

RESEARCH INTERESTS:
Current research is focusing on two different aspects of the biochemistry and molecular biology of gene expression.

Project 1 is a study of transcription elongation by RNA polymerase II. Gene expression can be controlled by governing the ability of RNA polymerase to transcribe a full-length RNA transcript. We have studied the function of elongation factor SII which activates a nuclease activity in RNA polymerase II that enables it to synthesize full length RNAs. Our focus now has been toward the in vivo role of this factor. We are employing the yeast S. cerevisiae to study elongationally compromised strains which are defective in transcribption of an enzyme important in nucleotide metabolism, IMP dehydrogenase. The transcription of this gene is regulated in a complex manner in response to cellular nucleotide pools and growth state through elongation control. This enzyme is the target of immunosuppressive drugs in patients receiving allografts such as kidney transplants. We are examining the means by which yeast become resistant to this drug and are turning our attention to the clinical situation with respect to patients receiving this drug.

Project 2 is a collaborative investigation into the fragile X syndrome which is the most common form of inherited mental retardation. The disease results from a CGG triplet repeat expansion mutation in the 5' untranslated region of FMR1 which results in the subsequent methylation and silencing of the gene. We are studying the mechanism by which FMR1 gene is transcribed in healthy individuals, as well as why it is inactivate in patients with the syndrome. We have identified a change in the chromatin structure of FMR1 concomitant with the mutation and methylation of the gene. Histones H3 and H4 at the FMR1 promoter, which are acetylated in normal cells, are hypoacetylated and methylated in patient cells. The identification and interaction of FMR1 transcription factors with a histone acetyltransferase is under investigation. We have been successful in identifying a number of transcription factors that run the gene under normal circumstances but which are absent from the mutated and silenced gene in patients.


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