WELCOME TO THE STRUHL LAB
Harvard Medical School
Department of Biological Chemistry and Molecular Pharmacology (BCMP)
240 Longwood Ave., Building C2, Rooms 315-325
Boston, MA 02115
The molecular mechanisms of transcriptional regulation are highly conserved among eukaryotes. Transcriptional regulation in response to environmental and developmental cues is mediated by the combinatorial and synergistic action of specific DNA-binding activators and repressors on components of the general transcription machinery and chromatin modifying activities. Much of the work in this laboratory combines genetic, molecular, and genomic approaches available in yeast to address fundamental questions about transcriptional regulatory mechanisms in living cells. In addition, we are defining physiological targets of human transcriptional regulatory proteins and chromatin modifications on a whole-genome basis using a novel microarray approach.
Transcriptional mechanisms in yeast: Current projects include 1) growth-regulated expression of ribosomal protein genes and activator-specific recruitment of TFIID, 2) novel aspects of signal transduction and gene regulation that occur during the response to osmotic stress, 3) how specific components of the basic transcription machinery are recruited to promoters in vivo under genetically and environmentally defined conditions, 4) mechanisms of global repression and gene silencing.
Relationship between chromatin structure and gene expression: Questions of interest include 1) the molecular basis for the relationship between histone acetylation and methylation with transcriptional activity, 2) genome-wide chromatin immunoprecipitation to determine whether and how individual nucleosome remodeling or histone modifying complexes are recruited to specific promoters, 3) a novel mechanism by which promoter regions are more accessible to nuclear proteins than non-promoter regions, 4) dynamics of chromatin modification in vivo .
Functional genomics in mammalian cells: In collaboration with Affymetrix, we are using novel microarrays that represent sequences of entire human chromosomes (soon to be the entire genome) to determine the in vivo binding sites of transcription factors (so far Myc, p53, and Sp1). Current emphasis is on obtaining whole chromosome maps of histone modifications, transcriptional silencing proteins, and oncoprotein and tumor suppressor proteins.
