Differential tissue specific, temporal and spatial expression patterns of the Aggrecan gene is modulated by independent enhancer elements.
Differential tissue specific, temporal and spatial expression patterns of the Aggrecan gene is modulated by independent enhancer elements.
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Aggrecan基因的差分组织特异性，时间和空间表达模式由独立增强子元素调节。
DOI：
10.1038/s41598-018-19186-4
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发表时间：
2018-01-17
影响因子：
4.6
通讯作者：
Bou-Gharios G
中科院分区：
文献类型：
--
作者：
Li IMH;Liu K;Neal A;Clegg PD;De Val S;Bou-Gharios G
软骨细胞控制软骨组织的空间和时间组成的转录机制在很大程度上仍然是难以捉摸的。本研究的主要目的是确定转录增强子是否在软骨组织中的软骨细胞的组织中发挥作用。我们专注于聚集蛋白聚糖基因（Acan），因为它对软骨的正常结构和功能至关重要，并且在软骨细胞成熟的不同阶段发育表达。在小鼠中使用转基因报告基因研究，我们确定了四个元素，其中两个显示出个体软骨细胞发育阶段特异性。特别是，一个增强子（-80）通过在成人软骨中主要活跃而与其他增强子区分开来。此外，-62元件独特地驱动早期软骨细胞中的报告活性。其余的软骨细胞特异性增强子+28和-30对软骨细胞类型没有偏好。转录因子SOX 9在体外与所有增强子相互作用，其中一个增强子（-30）中SOX 9结合位点的突变导致其软骨细胞特异性和异位增强子报告活性的丧失。因此，Acan增强子在不同发育阶段和成年期的软骨类型中协调该基因的精确时空表达。
The transcriptional mechanism through which chondrocytes control the spatial and temporal composition of the cartilage tissue has remained largely elusive. The central aim of this study was to identify whether transcriptional enhancers played a role in the organisation of the chondrocytes in cartilaginous tissue. We focused on the Aggrecan gene (Acan) as it is essential for the normal structure and function of cartilage and it is expressed developmentally in different stages of chondrocyte maturation. Using transgenic reporter studies in mice we identified four elements, two of which showed individual chondrocyte developmental stage specificity. In particular, one enhancer (−80) distinguishes itself from the others by being predominantly active in adult cartilage. Furthermore, the −62 element uniquely drove reporter activity in early chondrocytes. The remaining chondrocyte specific enhancers, +28 and −30, showed no preference to chondrocyte type. The transcription factor SOX9 interacted with all the enhancers in vitro and mutation of SOX9 binding sites in one of the enhancers (−30) resulted in a loss of its chondrocyte specificity and ectopic enhancer reporter activity. Thus, the Acan enhancers orchestrate the precise spatiotemporal expression of this gene in cartilage types at different stages of development and adulthood.
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影响因子：
64.8
作者：
Jin, Fulai;Li, Yan;Dixon, Jesse R.;Selvaraj, Siddarth;Ye, Zhen;Lee, Ah Young;Yen, Chia-An;Schmitt, Anthony D.;Espinoza, Celso A.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4
作者：
Barolo, Scott
通讯作者：
Barolo, Scott
影响因子：
14.9
作者：
FORRESTER, WC;TAKEGAWA, S;GROUDINE, M
通讯作者：
GROUDINE, M
影响因子：
11.4
作者：
Lefebvre, V;Li, P;de Crombrugghe, B
通讯作者：
de Crombrugghe, B