Human SWI/SNF drives sequence-directed repositioning of nucleosomes on C-myc promoter DNA minicircles.
The human SWI/SNF (hSWI/SNF) ATP-dependent chromatin remodeling complex is a tumor suppressor and essential transcriptional coregulator. SWI/SNF complexes have been shown to alter nucleosome positions, and this activity is likely to be important for their functions. However, previous studies have largely been unable to determine the extent to which DNA sequence might control nucleosome repositioning by SWI/SNF complexes. Here, we employ a minicircle remodeling approach to provide the first evidence that hSWI/SNF moves nucleosomes in a sequence dependent manner, away from nucleosome positioning sequences favored during nucleosome assembly. This repositioning is unaffected by the presence of DNA nicks, and can occur on closed-circular DNAs in the absence of topoisomerases. We observed directed nucleosome movement on minicircles derived from the human SWI/SNF-regulated c-myc promoter, which may contribute to the previously observed "disruption" of two promoter nucleosomes during c-myc activation in vivo. Our results suggest a model wherein hSWI/SNF-directed nucleosome movement away from default positioning sequences results in sequence-specific regulatory effects.
Sims
Hillel I
HI
Department of Biochemistry, Tufts University Sackler School of Graduate Biomedical Sciences, Boston, Massachusetts 02111, USA.
Lane
Jacqueline M
JM
Ulyanova
Natalia P
NP
Schnitzler
Gavin R
GR
D000818:Animals; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004270:DNA, Circular / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008957:Models, Genetic; D009707:Nucleosomes / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus
D002868:Chromosomal Proteins, Non-Histone; D004270:DNA, Circular; D009707:Nucleosomes; D016271:Proto-Oncogene Proteins c-myc; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors