Investigators and Program Directors
Randall H. Morse
Research Scientist, Wadsworth Center, Molecular Genetics
Professor, School of Public Health, Biomedical Sciences
Ph.D., California Institute of Technology
Postdoctoral training, Columbia University and National
Institutes of Health
E-mail: morse@wadsworth.org
Research Interests
Transcription in chromatin. DNA (white ribbon) is wrapped around a histone protein core (yellow discs) in chromatin. Transcription occurs when an activator binds a specific region of DNA and recruits transcription factors (TAFs, TBP, and others) and protein complexes (SWI/SNF and others) that modify histones or remodel chromatin.
DNA in eukaryotes is packaged into chromatin, creating a potentially formidable barrier to binding of proteins that are involved in transcription. Research over the past 15 years has revealed two ways in which chromatin is altered to allow transcription to proceed. First, histones can be modified by enzymes that methylate, acetylate, phosphorylate or perform other post-translational modifications that alter interactions between histones and transcription factors. Second, nucleosomes can be "remodeled" by specific enzyme complexes to alter the accessibility of the associated DNA. Deficiencies in either of these processes can affect gene regulation in organisms from yeast, which we use as a model system, to humans, where they have been implicated in pediatric cancers and developmental defects. Most of the proteins involved in chromatin and transcription are highly conserved between yeast and humans, making yeast a genetically tractable and appropriate model system.
A recent focus in the lab has been on the CHA1 gene as a model for studying changes in chromatin that accompany transcriptional regulation. This gene is easy to activate (by adding serine to growth medium), and undergoes chromatin remodeling upon its activation. We have learned that an unstructured region of histone H3 (one of the four histone proteins present in the nucleosome) that contains a number of sites for post-translational modification is needed to keep the CHA1 gene repressed in the absence of serine. We are currently investigating the sequence of histone modifications and chromatin remodeling events that accompany CHA1 activation, and the role of specific transcription factors in these events. We have also used microarray technology to investigate the roles of the histones in genome-wide transcriptional regulation.
Data from our microarray studies can be downloaded HERE.
Contact Information
Phone: 518-486-3116
Fax: 518-402-2299
E-mail: morse@wadsworth.org.