Yamini Dalal

Biography

Dr. Yamini Dalal became interested in chromosome structure and epigenetic gene regulation during her Baccalaureate years at St. Xavier's College, Bombay, India, where she graduated with a double major in Biochemistry and Life Sciences in 1995. She moved to the United States for her post-graduate work. In Arnold Stein's laboratory at Purdue University, she used classical chromatin biochemistry tools to understand how DNA sequence motifs can shape the chromatin structure. During this time, she discovered that the regions of the mouse genome contained alternating tracts of stiff and flexible DNA, which allowed in silico prediction of nucleosome positions. These positions could be recapitulated in vitro using just purified histones and DNA, and detected in vivo, at developmentally regulated genes in mice. She also studied how linker histone H1 could influence nucleosome positioning and chromatin folding in vitro and in vivo. For these studies, she received her Ph.D. from Purdue University in 2003. Histone variants were the next logical step in teasing out how intrinsic variability in the chromatin fiber can encode a diversity of biological functions. To study this aspect of chromatin structure, Yamini moved to Seattle to work with Dr. Steven Henikoff at the Fred Hutchinson Cancer Research Center from 2003-2007. Using a range of biochemical analyses, she and colleagues uncovered that the Drosophila centromere-specific histone variant makes non-canonical nucleosomes, features of which are reminiscent of the ancestral nucleosomes seen in the archaebacteria. Recent work from her lab has shown that some of these unusual features are conserved in human cells, that centromeric nucleosomes oscillate in structure and in modifications over the cell cycle. Such oscillations are perturbed in human cancers wherein CENP-A is innately mis-regulated and occupies ectopic regions of the human genome linked to instability. We are now expanding our studies to other histone variants in human tumors.

Research Interest

1) Chromatin structure 2) Protein biochemistry 3) Molecular genetics 4) Cell biology 5) Atomic force microscopy 6) Cancer biology 7) How CenH3 nucleosome structure varies through the cell cycle, 8) How assembly and disassembly kinetics influence the centromeric chromatin fiber accessibility and uniformity, 9) How the global chromatin fiber's three-dimensional arrangement and structure is altered when the individual nucleosomes that make up the fiber are replaced by CenH3 or other histone variants in colorectal tumors, 10) Functional and epigenetic consequences of histone variant invasion of ectopic loci, and 11) Whether the distinctive features we observe in fly and human are conserved in other species.  Cell Biology:  A long noncoding RNA helps cells divide  Dr. Dalal's this research was recently highlighted in Science.