Genes function in the context of chromosomes in living cells and Dr. Michael Grunstein's laboratory studies how chromosomal structures regulate gene activity. Grunstein and his colleagues have found that histones regulate genes quite differently when genes are in euchromatin as opposed to heterochromatin. The researchers believe that these differences are due to the interaction of histones with different trans-acting regulatory proteins.
A major goal in Grunstein's laboratory is to define how histones and their post-translational modifications interact with such factors to regulate gene activity, DNA replication and the heterochromatin structure and function of telomeres. To study these problems they use the biochemistry, genetics, recombinant DNA and genome wide DNA microarray technologies available in the yeast Saccharomyces cerevisiae. These results are then applied to questions relating to human cell differentiation. Using human genome wide approaches and RNAi screens for human genes that affect histone modifications the lab studies how histone modifications regulate the genetic program of pluripotency in human stem cells.
Selected Cancer-Related Publications:
Kitada T, Schleker T, Sperling AS, Xie W, Gasser SM, Grunstein M. gammaH2A is a component of yeast heterochromatin required for telomere elongation. Cell Cycle. 2011 Jan 15;10(2):293-300. Epub 2011 Jan 15.
Xie W, Song C, Young NL, Sperling AS, Xu F, Sridharan R, Conway AE, Garcia BA, Plath K, Clark AT, Grunstein M. Histone h3 lysine 56 acetylation is linked to the core transcriptional network in human embryonic stem cells. Mol Cell. 2009 Feb 27;33(4):417-27.
Seligson DB, Horvath S, Shi T, Yu H, Tze S, Grunstein M, Kurdistani SK. Global histone modification patterns predict risk of prostate cancer recurrence. Nature. 2005; 435(7046): 1262-6.
Xu F, Zhang K, Grunstein M. Acetylation in histone H3 globular domain regulates gene expression in yeast. Cell. 2005; 121(3): 375-85.
Kurdistani SK, Tavazoie S, Grunstein M. Mapping global histone acetylation patterns to gene expression. Cell. 2004; 117(6): 721-33.