Dr. Yamini Dalal

The eukaryotic genome is organized within a structural matrix composed of histones and DNA, both of which are structurally conserved over millions of years of evolution. Surprisingly, for all this conservation, there is a vast amount of epigenetic variation brought about by simple modifications and substitutions of the histones within the unit nucleosomes that make up chromatin.
I am interested in understanding the mechanistic basis underlying chromatin's variability, and how this variation contributes epigenetically to eukaryotic biology.
I have studied two facets of this problem. In my graduate work, I elucidated simple sequence rules that allow nucleosomes to position along the DNA fiber and showed that the positions could be computationally predicted and biochemically validated. Furthermore, these sequence rules appear to work in vivo within a specific fraction of the mouse genome enriched in housekeeping genes, suggesting that how chromatin is organized has a discrete role in gene function.
More recently, I turned my attention to centromeres- these are absolutely required parts of chromosomes that attach to microtubules and assist in segregation of the genome during mitosis and meiosis. Although centromeres have been visualized by light microscopy for over a century and studied genetically for the past 30 years, the primary structure and inheritance of centromeres has been a mystery. Using chromatin biochemistry, proteomics, electron and atomic force microscopies, we demonstrated that centromeric chromatin is fundamentally distinct from the rest of the chromosome at the most basic unit of organization- the centromeric nucleosome. We elucidated properties of this highly specialized chromatin that can be directly connected to observed features of its biological function. We also observed that the organization of the centromere is similar to chromatin found in ancient organisms called the archaebacteria. These organisms predate the evolutionary split between eukarya and prokarya, and have the earliest type of chromatin, suggesting that centromeres, and correspondingly, their associated biological functions must have arisen at the very dawn of eukaryotic evolution.
I am interested in pursuing how this unusual centromeric nucleosome connects to other kinetochore proteins that comprise the centromere, and understanding how the resulting chromatin-complexed structure may contribute to epigenetic inheritance of centromeres.