Michael Grunstein, Ph.D.
/in /by Grant Alkin
Email Address:
mg@mbi.ucla.edu
Office Phone Number:
(310) 825-0840
Website
Grunstein Lab
Office Address:
Boyer Hall 302
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 sites are a cause, or a result, of transcription. In the early 1980s, the Grunstein lab pioneered the use of genetics in analyzing histone protein function in yeast. This analysis showed 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 and spread of heterochromatin, as well as how the site acts as a barrier to heterochromatin’s spread.
The Grunstein laboratory used genetics, as well as genome-wide and gene-specific biochemical approaches, to study how histones regulate the binding of regulatory enzymes and structural factors to chromatin. The 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. 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 lab analyzed the modification of this site – which also regulates yeast histone assembly, DNA replication and DNA repair – and its role in the differentiation of human stem cells.