SOX9 regulates multiple genes in chondrocytes, including genes encoding ECM proteins, ECM modification enzymes, receptors, and transporters.
SOX9 regulates multiple genes in chondrocytes, including genes encoding ECM proteins, ECM modification enzymes, receptors, and transporters.
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DOI：
10.1371/journal.pone.0107577
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发表时间：
2014
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;Lu Y;Liang S;Mori-Akiyama Y;Chen D;de Crombrugghe B;Yasuda H
转录因子SOX 9在决定几种细胞类型的命运中起重要作用，并且是调节软骨细胞发育的主要因子。我们的目的是确定软骨细胞基因组中哪些基因直接或间接受SOX 9控制。我们使用RNA-Seq来鉴定其表达水平受SOX 9影响的基因，并使用SOX 9 ChIP-Seq来鉴定那些含有SOX 9相互作用位点的基因。对于RNA-Seq，将用Ad-CMV-Cre感染的原代Sox 9 flox/flox小鼠软骨细胞的RNA表达谱与用对照腺病毒感染的相同细胞的RNA表达谱进行比较。RNA-Seq数据的分析表明，当用Ad-CMV-Cre感染使Sox 9 mRNA的水平降低超过8倍时，196个基因显示表达降低至少4倍。这些包括许多软骨细胞外基质（ECM）基因和ECM修饰酶（转移酶）、膜受体、转运蛋白等的许多基因。在ChIP-Seq中，75%的SOX 9相互作用位点在峰顶部的100 bp内具有典型的反向重复基序。在55%的基因中发现了SOX 9相互作用位点，这些基因的表达在SOX 9耗尽的细胞中降低超过8倍，并且在较少的基因中发现了其表达降低超过4倍，这表明这些是SOX 9的直接靶点。RNA-Seq和ChIP-Seq的结合提供了对软骨细胞的SOX 9控制的遗传程序的更全面的理解。
The transcription factor SOX9 plays an essential role in determining the fate of several cell types and is a master factor in regulation of chondrocyte development. Our aim was to determine which genes in the genome of chondrocytes are either directly or indirectly controlled by SOX9. We used RNA-Seq to identify genes whose expression levels were affected by SOX9 and used SOX9 ChIP-Seq to identify those genes that harbor SOX9-interaction sites. For RNA-Seq, the RNA expression profile of primary Sox9flox/flox mouse chondrocytes infected with Ad-CMV-Cre was compared with that of the same cells infected with a control adenovirus. Analysis of RNA-Seq data indicated that, when the levels of Sox9 mRNA were decreased more than 8-fold by infection with Ad-CMV-Cre, 196 genes showed a decrease in expression of at least 4-fold. These included many cartilage extracellular matrix (ECM) genes and a number of genes for ECM modification enzymes (transferases), membrane receptors, transporters, and others. In ChIP-Seq, 75% of the SOX9-interaction sites had a canonical inverted repeat motif within 100 bp of the top of the peak. SOX9-interaction sites were found in 55% of the genes whose expression was decreased more than 8-fold in SOX9-depleted cells and in somewhat fewer of the genes whose expression was reduced more than 4-fold, suggesting that these are direct targets of SOX9. The combination of RNA-Seq and ChIP-Seq has provided a fuller understanding of the SOX9-controlled genetic program of chondrocytes.
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影响因子：
11.4
作者：
Lefebvre, V;Li, P;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
5.3
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Lefebvre, V;Huang, WD;deCrombrugghe, B
通讯作者：
deCrombrugghe, B
影响因子：
64.5
作者：
Arango, NA;Lovell-Badge, R;Behringer, RR
通讯作者：
Behringer, RR
影响因子：
4.8
作者：
Hoang, B;Moos, M;Luyten, FP
通讯作者：
Luyten, FP