Nucleic Acids Research Advance Access originally published online on April 28, 2009
Nucleic Acids Research 2009 37(12):3897-3911; doi:10.1093/nar/gkp261
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Nucleic Acids Research, 2009, Vol. 37, No. 12 3897-3911
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gene Regulation, Chromatin and Epigenetics |
Remodeling of chromatin structure within the promoter is important for bmp-2-induced fgfr3 expression
1Institute of Genetic Engineering, Jinan University; National Engineering Research Center of Genetic Medicine, Key Lab for Genetic Medicine of Guangdong Province, Guangzhou, Guangdong, 510632, 2Shaoguan Tielu Hospital, Shaoguan, Guangdong, 512023, 3Medical Research Center, No. 2 Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510120, PR China and 4MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK
*To whom correspondence should be addressed. Tel: +86 20 85221983; Fax: +86 20 85221983; Email: hongan_gz{at}163.com
Received November 15, 2008. Revised April 8, 2009. Accepted April 8, 2009.
Fibroblast growth factor receptor 3 (FGFR3) plays an important role in cartilage development. Although upregulation of FGFR3 expression in response to bone morphogenetic protein-2 (BMP-2) has been reported, the molecular mechanisms remain unknown. In this study, we used in vivo approaches to characterize BMP-2-induced alterations in the chromatin organization of the FGFR3 core promoter. Chromatin immunoprecipitation analysis demonstrated that the binding of Brg1, a component of the SWI/SNF remodeling complex, may selectively remodel a chromatin region (encompassing nucleotide –90 to +35), uncovering the transcription start site and three Sp1-binding sites, as revealed by nuclease digestion hypersensitivity assays. We then showed an increase in the association of Sp1 with the proximal promoter, followed by the recruitment of p300, resulting in a change of the histone ‘code’, such as in phosphorylation and methylation. Collectively, our study results suggest a model for BMP-2-induced FGFR3 expression in which the core promoter architecture is specifically regulated.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.