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Molecular and Cellular Biology, April 2006, p. 2550-2559, Vol. 26, No. 7
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.7.2550-2559.2006

Cooperative Activity of BRG1 and Z-DNA Formation in Chromatin Remodeling

Hong Liu,1 Niveen Mulholland,1 Haiqing Fu,2 and Keji Zhao1*

Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892,1 Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 208922

Received 26 September 2005/ Returned for modification 2 December 2005/ Accepted 11 January 2006

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.

* Corresponding author. Mailing address: Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Building 10, Room 7N311, 9000 Rockville Pike, Bethesda, MD 20892-1674. Phone: (301) 496-2098. Fax: (301) 480-0961. E-mail: zhaok{at}nhlbi.nih.gov.

Molecular and Cellular Biology, April 2006, p. 2550-2559, Vol. 26, No. 7
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.7.2550-2559.2006




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