来自中山大学附属第二医院的研究人员以多种实验方法，研究工具为基础，发现了重要转录因子Sox9的一个分子机制，这对于研究骨形成具有重要意义。这一研究成果公布在Biochem Biophys Res Commun.上。
在这篇最新的文章中，研究人员围绕着Sox9展开了研究，利用各种研究手段发现了之前未知的一种分子机制。
Sox9是软骨形成（chondrogenesis）过程中一个十分关键的转录因子，虽然已经有研究表明骨形成蛋白2(bone morphogenetic protein 2,BMP2)能诱导Sox9的表达，但是其中的机制至今并不清楚。
研究人员利用体内实验的方法对BMP2诱导的Sox9关键启动子周围的染色体组织的变化进行了分析，通过BMP2诱导后核酸酶超敏位点图谱，研究人员发现Sox9近侧启动子存在一个诱导性的超敏位点，而免疫共沉实验则证明BMP2能增加转录因子NF－Y与组蛋白去甲基转移酶p300/CBP的关联。并且研究人员还发现BMP2诱导能引起Sox9基因处的组蛋白乙酰化和甲醇化。
这些研究结果表明Sox9基因由BMP2诱导的转录活性与染色体和组蛋白的变化有关。（生物谷Bioon.com）
相关介绍：染色质免疫沉淀法（Chromatin immunoprecitation，ChIP）是研究体内DNA与蛋白质相互作用的重要工具。它可以灵敏地检测目标蛋白与特异DNA片段的结合情况，还可以用来研究组蛋白与基因表达的关系。核小体组蛋白可以发生多种翻译后的共价修饰，如乙酰化、甲基化、磷酸化、泛素化等，这些共价修饰与真核基因的表达密切相关。根据“组蛋白密码”假说，组蛋白的各种共价修饰的组合会以协同或拮抗的方式诱导特异的下游生物学功能，因此，ChIP也为研究组蛋白修饰在基因表达中的作用，全面阐明真核基因的表达调控机制提供了强有力的研究工具。
中国第一ChIP论坛：ChIP Forum
生物谷推荐原始出处：
Biochemical and Biophysical Research Communications doi:10.1016/j.bbrc.2008.12.062
Bone Morphogenetic Protein-2 induces chromatin remodeling and modification at the proximal promoter of Sox9 gene
Qiuhui Pana, Yanfeng Wua, Tianxin Lina, Herui Yaob, Zhonghan Yange, Guoquan Gaoe, Erwei Songc, , and Huiyong Shend, ,
aMedical Research Center, No. 2 Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, PR China
bDepartment of Cancer, No. 2 Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, PR China
cDepartment of Breast Surgery, No. 2 Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, PR China
dDepartment of Orthopedics, No. 2 Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, PR China
eDepartment of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, PR China
Abstract
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.
