Albany 2013: Book of Abstracts

category image Albany 2013
Conversation 18
June 11-15 2013
©Adenine Press (2012)

Packaging Trinucleotide Repeats: The effect of CAG/CTG Repeats On Nucleosome Formation

In neurological diseases such as fragile X syndrome, spinal and bulbar muscular atrophy, myotonic dystrophy, and Huntington’s disease, the molecular basis of pathogenicity is the presence of an expanded Trinucleotide Repeat (TNR) tract (Ashley and Warren, 1995). TNRs implicated in many of these diseases are composed of CAG/CTG repeats. For example, in healthy individuals 5-35 CAG/CTG TNR repeats are present in the huntingtin gene. However, individuals with 40 or greater repeats will develop Huntington’s disease (Andrew, et al., 1993). We are particularly interested in how these TNR sequences are packaged in chromatin. Recent evaluations of CAG/CTG TNR sequences in our laboratory have demonstrated that the repeats increase the propensity for the DNA sequences to incorporate into nucleosomes, where nucleosomes represent the minimal unit of packaging in chromatin (Volle and Delaney, 2012). In this work we are interested in determining the minimum number of CAG/CTG repeats required to confer a significant increase in nucleosome incorporation relative to sequences that lack the TNR sequence. By defining the changes imposed on these fundamental interactions by the presence of a CAG/CTG repeat tract, we will gain insight into the possible interactions that allow for the expansion of these TNR tracts.

This work was supported by the National Institute of Environmental Health Sciences (R01ES019296) and the Brown IMSD program, which is funded by NIGMS grant R25GM083270.


    Ashley Jr, C. T., and Stephen T. Warren, S. T. (1995). Trinucleotide repeat expansion and human disease. Annual review of genetics 29, 703-728

    Andrew, S. E., et al. (1993) The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nature genetics 4. 398-403.

    Volle, C. B., and Delaney, S. (2012).CAG/CTG Repeats Alter Affinity for the Histone Core and Positioning of DNA in the Nucleosome. Biochemistry 51 9814–9825

Vilma Medrano
Sarah Delaney

Department of Molecular Biology
Cellular Biology, and Biochemistry
Brown University
Providence, RI 02906

Ph. 401-863-2044
Fax. 401-863-1993