Bone morphogenetic protein-2 induces chromatin remodeling and modification at the proximal promoter of Sox9 gene.
Sox9 is a key transcription factor which plays an important role in chondrogenesis. Although Bone Morphogenetic Protein-2 (BMP-2) has been reported to induce Sox9 expression, the underlying molecular mechanism remains elusive. Here, we used in vivo approaches to characterize BMP-2-induced alterations in chromatin organization around the Sox9 core promoter. Nuclease hypersensitive site mapping following BMP-2 stimulation showed an inducible hypersensitive site in the Sox9 proximal promoter. Immunoprecipitation (IP) experiments demonstrated that BMP-2 increased the association of the transcription factor NF-Y with histone acetyltransferase p300/CBP. Chromatin immunoprecipitation (ChIP) analysis showed the binding of the NF-Y-p300 complex to the Sox9 gene proximal promoter along with PCAF and RNA polymerase II. We also found that BMP-2 stimulation caused histone hyperacetylation and methylation at the Sox9 gene. Collectively, these data suggest that the activation of Sox9 gene transcription by BMP-2 is associated with chromatin remodeling and histone modification.
Pan
Qiuhui
Q
Medical Research Center, No. 2 Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, PR China.
Wu
Yanfeng
Y
Lin
Tianxin
T
Yao
Herui
H
Yang
Zhonghan
Z
Gao
Guoquan
G
Song
Erwei
E
Shen
Huiyong
H
D000107:Acetylation; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism* / Q000494:pharmacology; D023081:CCAAT-Binding Factor / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D004262:DNA Restriction Enzymes / Q000737:chemistry; D003850:Deoxyribonuclease I / Q000737:chemistry; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D047468:Immunoprecipitation; D051379:Mice; D011401:Promoter Regions, Genetic; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors / Q000378:metabolism
D055396:Bone Morphogenetic Protein 2; D023081:CCAAT-Binding Factor; D006657:Histones; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D050880:p300-CBP Transcription Factors; D051498:Receptor, Fibroblast Growth Factor, Type 3; D004262:DNA Restriction Enzymes; D003850:Deoxyribonuclease I