Identification of SOX9 interaction sites in the genome of chondrocytes.
Identification of SOX9 interaction sites in the genome of chondrocytes.
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DOI：
10.1371/journal.pone.0010113
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发表时间：
2010-04-09
期刊：
影响因子：
3.7
通讯作者：
Yasuda H
中科院分区：
文献类型：
--
作者：
Oh CD;Maity SN;Lu JF;Zhang J;Liang S;Coustry F;de Crombrugghe B;Yasuda H
我们之前的工作提供了强有力的证据，证明转录因子 SOX9 是软骨分化和软骨形成所必需的，在这种分化中充当“主开关”。 SOX9 的杂合突变会导致软骨发育不良，这是一种严重的人类骨骼畸形综合征，其特征是软骨内骨普遍发育不全。为了深入了解 SOX9 用于控制软骨细胞中靶基因网络的逻辑，我们使用 SOX9 抗体进行了 ChIP 芯片实验。 ChIP DNA 与微阵列杂交，该微阵列涵盖 80 个基因，其中许多基因与软骨细胞分化有关。在一系列软骨细胞外基质 (ECM) 基因（包括 Col2a1、Col11a2、Aggrecan 和 Cdrap）以及特定转录因子和信号分子的基因中检测到杂交峰。我们的结果还显示了编码增强 SOX9 转录活性的蛋白质的基因中的 SOX9 相互作用位点。有趣的是，在 Col1a1 和 Osx 等基因中也观察到了强烈的 SOX9 信号，它们的表达在软骨细胞中强烈下调，但在成骨细胞中表达较高。在 Col2a1 基因中，除了在内含子 1 中先前鉴定的增强子上有一个相互作用位点外，在内含子 6 中还发现了另一个强相互作用位点。该位点不含核小体，特别是在软骨细胞中，表明该位点在 SOX9 的 Col2a1 转录调节中发挥着重要作用。我们的结果提供了对分化“主”转录因子控制软骨细胞遗传程序所使用的策略的广泛理解。
Our previous work has provided strong evidence that the transcription factor SOX9 is completely needed for chondrogenic differentiation and cartilage formation acting as a “master switch” in this differentiation. Heterozygous mutations in SOX9 cause campomelic dysplasia, a severe skeletal dysmorphology syndrome in humans characterized by a generalized hypoplasia of endochondral bones. To obtain insights into the logic used by SOX9 to control a network of target genes in chondrocytes, we performed a ChIP-on-chip experiment using SOX9 antibodies. The ChIP DNA was hybridized to a microarray, which covered 80 genes, many of which are involved in chondrocyte differentiation. Hybridization peaks were detected in a series of cartilage extracellular matrix (ECM) genes including Col2a1, Col11a2, Aggrecan and Cdrap as well as in genes for specific transcription factors and signaling molecules. Our results also showed SOX9 interaction sites in genes that code for proteins that enhance the transcriptional activity of SOX9. Interestingly, a strong SOX9 signal was also observed in genes such as Col1a1 and Osx, whose expression is strongly down regulated in chondrocytes but is high in osteoblasts. In the Col2a1 gene, in addition to an interaction site on a previously identified enhancer in intron 1, another strong interaction site was seen in intron 6. This site is free of nucleosomes specifically in chondrocytes suggesting an important role of this site on Col2a1 transcription regulation by SOX9. Our results provide a broad understanding of the strategies used by a “master” transcription factor of differentiation in control of the genetic program of chondrocytes.
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DOI：
10.1073/pnas.0407510102
发表时间：
2005-02-15
影响因子：
11.1
作者：
Kawakami, Y;Tsuda, M;Asahara, H
通讯作者：
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影响因子：
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作者：
Ioshikhes, Ilya P.;Albert, Istvan;Pugh, B. Franklin
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作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
DOI：
10.1073/pnas.0504750102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Akiyama, H;Kim, JE;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
4.6
作者：
Ivkovic, S;Yoon, BS;Lyons, KM
通讯作者：
Lyons, KM