Generation and interconversion of multiple distinct nucleosomal states as a mechanism for catalyzing chromatin fluidity.
We have dissected the steps in nucleosome remodeling by BRG1, the ATPase subunit of human SWI/SNF. BRG1-catalyzed DNA exposure is not enhanced by the proximity of the site to the ends of nucleosomal DNA, suggesting that the mechanism involves more than peeling or sliding of the DNA. Comparison of DNA exposure at specific sites with overall changes in the path of DNA implies that BRG1 generates multiple distinct remodeled structures and continuously interconverts them. These characteristics are shared by the entire SWI/SNF complex and have parallels, as well as interesting differences, with the activities of GroEL and Hsp70 protein chaperones. The chaperone-like activity of SWI/SNF is expected to create multiple opportunities for the binding of distinct regulatory factors, providing one mechanism by which SWI/SNF family complexes can contribute to both activation and repression of transcription.
Narlikar
G J
GJ
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Phelan
M L
ML
Kingston
R E
RE
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D046911:Macromolecular Substances; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D009687:Nuclear Proteins / Q000378:metabolism*; D023282:Nuclease Protection Assays; D009707:Nucleosomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits; D013816:Thermodynamics; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D002843:Chromatin; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D009707:Nucleosomes; D021122:Protein Subunits; C499336:SMARCA1 protein, human; C084011:SMARCA2 protein, human; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D004247:DNA; D003850:Deoxyribonuclease I; C024388:CTGCAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; C084108:SMARCA4 protein, human; D004265:DNA Helicases