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Academic Background

Peterson Lab Web Page

Craig Peterson received his BS from the University of Washington in 1983 and his PhD from the University of California, Los Angeles in 1988. He was a Helen Hay Whitney Foundation postdoctoral fellow from 1988-1991, in the Department of Biochemistry and Biophysics at the University of California, San Francisco. In 1992, he joined the University of Massachusetts Medical School as a faculty member in the Program in Molecular Medicine.

How chromosome structure influences nuclear processes

craig peterson's picture The overall objective of our research is to determine how chromosome structure influences nuclear processes and to identify and characterize the cellular machines that contend with this structure.Over the years, our general strategy has been to employ yeast molecular genetics to develop detailed models that describe complex nuclear events that can then be directly tested and expanded by subsequent biophysical and biochemical approaches. Much of our efforts over the past few years have focused on ATP-dependent chromatin remodeling enzymes (e.g. SWI/SNF and INO80) that hydrolyze ~1,000 ATPs per minute to alter chromatin structure and thereby regulate transcription, DNA repair, or replication. Our studies are centered on both the regulation and mechanism of this chromatin "remodeling" reaction. Since most of these enzymes are enormous (>1 MDa), multi-subunit enzymes, we are also interested in understanding how these enzymes are assembled and what roles are played by individual subunits. To address these goals we use a broad spectrum of methodologies, including yeast molecular and classical genetics, modern analytical ultracentrifugation, molecular biology, and traditional biochemistry. Notably, these remodeling enzymes are conserved from yeast to mammals, play key roles in gene expression and the maintenance of genome integrity, and loss of their function leads to various disease states.

In addition to our studies on chromatin remodeling enzymes, we also wish to understand the dynamics of chromatin fibers and how fiber condensation influences DNA repair, transcription, and DNA replication. These projects involve the biochemical reconstitution of defined nucleosomal arrays from recombinant histones and DNA templates that contain head-to-tail repeats of nucleosome positioning sequences. Typically, we perform sedimentation velocity experiments in the analytical ultracentrifuge to investigate how histone modifications (e.g. H4 K16 acetylation), histone variants, or heterochromatin proteins (e.g. HP1, Sir3) influence the folding dynamics of these reconstituted chromatin fibers. These biophysical studies are complemented by powerful biochemical assays where we assess how the structure of a chromatin fiber regulates various steps of DNA double strand break repair or DNA replication.

As we learn more about the dynamics of chromatin fibers and the basic mechanics of DNA repair and DNA replication, we have initiated in vivo studies that probe how these processes are coordinated and regulated within cells. For instance, we have recently, found that a DNA double strand break can induce the re-localization of a chromosomal domain to the nuclear envelope and that this compartmentalization inhibits recombinational repair. Interestingly, localization to the nuclear periphery requires components of the telomerase complex and seems to be due to an attempt to heal the chromosome by formation of a new telomere. Similar types of chromosome healing events may also occur at stalled replication forks. We are currently using a variety of cell biological and molecular genetic approaches to dissect the complex decision-making processes that a cell employs in its attempts to maintain genome integrity.

Figure

Research Figure

Figure Legend

3 dimensional EM reconstruction of the 1.15 MDa yeast SWI/SNF chromatin remodeling complex (image courtesy of C. Woodcock and R. Horowitz). Top two panels show two views of yeast SWI/SNF -- dimensions are 27 nm by 8 nm. Bottom two panels show a theoretical docking of a mononucleosome core particle into the presumptive active site. Note the large cavity that provides a perfect fit for the nucleosome core when it is oriented with the entry/exit strands of DNA facing away from the SWI/SNF surface.

Peterson Lab Web Page
One or more keywords matched the following items that are connected to Peterson, Craig
Item TypeName
Academic Article The SIN domain of the histone octamer is essential for intramolecular folding of nucleosomal arrays.
Academic Article Rad54p is a chromatin remodeling enzyme required for heteroduplex DNA joint formation with chromatin.
Academic Article Creating designer histones by native chemical ligation.
Academic Article The SANT domain: a unique histone-tail-binding module?
Academic Article DNA instructed displacement of histones H2A and H2B at an inducible promoter.
Academic Article Promoter targeting and chromatin remodeling by the SWI/SNF complex.
Academic Article Polyamine analogues: potent inducers of nucleosomal array oligomerization and inhibitors of yeast cell growth.
Academic Article SWI/SNF is required for transcriptional memory at the yeast GAL gene cluster.
Academic Article Structural characterization of H3K56Q nucleosomes and nucleosomal arrays.
Academic Article G-less cassette in vitro transcription using HeLa cell nuclear extracts.
Academic Article Chromatin remodeling: nucleosomes bulging at the seams.
Academic Article Chromatin remodeling by the SWI/SNF complex is essential for transcription mediated by the yeast cell wall integrity MAPK pathway.
Academic Article HDAC's at work: everyone doing their part.
Academic Article Molecular biology. Chromatin higher order folding--wrapping up transcription.
Academic Article Essential role for the SANT domain in the functioning of multiple chromatin remodeling enzymes.
Academic Article Structural analysis of the yeast SWI/SNF chromatin remodeling complex.
Academic Article DNA repair choice defines a common pathway for recruitment of chromatin regulators.
Academic Article Cellular machineries for chromosomal DNA repair.
Academic Article Effects of HMGN1 on chromatin structure and SWI/SNF-mediated chromatin remodeling.
Academic Article Histone H4-K16 acetylation controls chromatin structure and protein interactions.
Academic Article The LRS and SIN domains: two structurally equivalent but functionally distinct nucleosomal surfaces required for transcriptional silencing.
Academic Article Swi3p controls SWI/SNF assembly and ATP-dependent H2A-H2B displacement.
Academic Article Mechanisms that regulate localization of a DNA double-strand break to the nuclear periphery.
Academic Article Opening the DNA repair toolbox: localization of DNA double strand breaks to the nuclear periphery.
Academic Article Dignam and Roeder nuclear extract preparation.
Academic Article Releasing the brakes on a chromatin-remodeling enzyme.
Concept Nuclear Proteins
Concept Molecular Structure
Concept Protein Structure, Tertiary
Concept Antigens, Nuclear
Concept Structure-Activity Relationship
Academic Article The Ino80 complex prevents invasion of euchromatin into silent chromatin.
Academic Article Structural analyses of the chromatin remodelling enzymes INO80-C and SWR-C.
Academic Article The Histone Chaperones FACT and Spt6 Restrict H2A.Z from Intragenic Locations.
Academic Article Cryo-EM structure of the human Sirtuin 6-nucleosome complex.
Academic Article Cryo-EM structure of the human Sirtuin 6-nucleosome complex.
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  • Structure