Nanoscale structure and dynamics of nucleosome arrays assembled on DNA templates with physiologically relevant sequences

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Chromatin dynamics define how chromatin assembles into higher order structures and its function. However, molecular details of the assembly mechanism remain unexplained, including the role of DNA sequence in chromatin organization, specifically the interactions of nucleosomes. The research will address this gap in knowledge by examining the effects of DNA sequence on the interplay between chromatin structure, dynamics and function. This project also facilitates integration of scientific and technological advances in graduate and undergraduate student education. For example, the concepts of DNA and single molecule biophysics are incorporated into a biophysical chemistry course, and the research offers training opportunities for students at all levels in the university. The PI is also a member of the state EPSCoR committee and participates in the Young Nebraska Scientists (YNS) program that provides STEM enrichment activities for middle and high school students.Interaction between nucleosomes is a fundamental property that defines the assembly and function of chromatin. The central hypothesis examined in this project is that DNA sequence is a critical factor in the interactions between nucleosomes and their assembly into higher order structures. Nanoscale structural studies will be conducted by single-molecule high-speed atomic force microscopy (AFM) to address the role of DNA sequence in canonical nucleosome interactions, in the conformational dynamics of centromere nucleosomes, and in the assembly of higher order structures of canonical and centromere nucleosome arrays. The outcomes will advance the knowledge of chromatin structure and dynamics at different levels of organization and yield new insights into function.This project is jointly funded by the Genetic Mechanisms and Molecular Biophysics programs of the Molecular and Cellular Biosciences Division in the Biological Sciences Directorate.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.