Research Interest:

Michael Grunstein studies how histones and their post-translational modifications regulate chromosomal functions. It had been known since the 1960s that histone acetylation and gene activity were correlated but it was not known whether changes in chromatin structure and in particular histone acetylation are a cause or result of transcription. The Grunstein lab pioneered the use of genetics in analyzing histone protein function in yeast in the early 1980s. This analysis was to show that nucleosomes are repressors of transcription initiation in living cells and that acetylation sites at the histone N termini are required for gene activity. Moreover his lab demonstrated in 1995 that non-histone regulatory proteins bind histones to regulate heterochromatin formation. This allowed the lab to determine how an acetylation site (histone H4 K16) at the H4 N terminus regulates the initiation, spreading and the barrier to spreading of heterochromatin.

At present the Grunstein laboratory uses genetics, genome wide and gene specific biochemical approaches to study how histones regulate the binding of regulatory enzymes and structural factors to chromatin. His lab's findings include the role of histone deacetylation in regulating the timing of DNA replication, the role of deacetylation in gene activity and the genome wide division of labor for histone deacetylases and histone acetylation sites in yeast. Recent studies from the Grunstein lab have uncovered the acetylation of a novel site histone H3 K56 in yeast and its role in transcription and heterochromatin silencing. The modification of this site that also regulates yeast histone assembly, DNA replication and DNA repair is currently a focus of the lab in studying the differentiation of human stem cells.

Detailed Biography:

Michael Grunstein is Distinguished Professor of Biological Chemistry at the Geffen School of Medicine at UCLA. He was born in Romania, obtained his BSc degree from McGill University in Montreal, the PhD degree from the University of Edinburgh, Scotland and did his post-doctoral training at Stanford University in Palo Alto, California where he invented the Colony Hybridization screening technique of recombinant DNAs in David Hogness's laboratory. Soon after coming to UCLA in 1975 he pioneered the genetic analysis of histones in yeast and showed for the first time that histones are regulators of gene activity in living cells. He now studies the means by which histone modifications regulate gene activity and DNA replication in yeast, mouse and human cells.