Cooperative activity of BRG1 and Z-DNA formation in chromatin remodeling.
The mammalian genome contains tens of thousands of CG and TG repeat sequences that have high potential to form the nonclassical left-handed double-helical Z-DNA structure. Previously we showed that activation of the colony-stimulating factor 1 (CSF1) gene by the chromatin remodeling enzyme, BRG1, results in formation of Z-DNA at the TG repeat sequence located within the promoter. In this report, we show that the TG repeats are assembled in a positioned nucleosome in the silent CSF1 promoter and that activation by BRG1 disrupts this nucleosome and results in Z-DNA formation. Active transcription is not required for the formation of Z-DNA but does result in an expanded region of Z-DNA. Formation of sequences by both BRG1 and the Z-DNA is required for effective chromatin remodeling of the CSF1 promoter. We propose the Z-DNA formation induced by BRG1 promotes a transition from a transient and partial remodeling to a more extensive disruption of the canonical nucleosomal structure. The data presented in this report establish that Z-DNA formation is an important mechanism in modulating chromatin structure, in similarity to the activities of ATP-dependent remodelers and posttranslational histone modifications.
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N311, 9000 Rockville Pike, Bethesda, Maryland 20892-1674, USA.
Hong
H
Liu
Niveen
N
Mulholland
Haiqing
H
Fu
Keji
K
Zhao
D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases; D043542:DNA, Z-Form / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000378:metabolism*; D009707:Nucleosomes / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D002843:Chromatin; D043542:DNA, Z-Form; D009687:Nuclear Proteins; D009707:Nucleosomes; D012333:RNA, Messenger; D014157:Transcription Factors; D016173:Macrophage Colony-Stimulating Factor; C084108:SMARCA4 protein, human; D004265:DNA Helicases