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Cell Reoports:调节机体软骨形成的蛋白

    近日国际杂志Cell Reoports发表来自东京大学等处的研究人员上的一篇研究论文,研究阐明了名为Sox9的蛋白质调节软骨产生的分子机制。表明软骨不仅可以帮助确定人体耳朵和鼻子的形状,其还可以帮助机体呼吸并且形成健康的骨质,而这过程对机体存活十分重要。


    研究者表示,研究揭示了软骨细胞被Sox9制造及维持的分子机理,Sox9蛋白可以以不同的方式同细胞中的DNA结合;在某些情况下,Sox9蛋白会成对儿存在,并且在分子修饰器存在的情况下直接同DNA结合,当特殊的Sox9结合发生在DNA上的多个位点时,其就会开启基因的表达使得细胞转变成为软骨细胞。


    当Sox9处于结合的过程中时,其和DNA并不会完美地进行结合,而研究者则假设,这种最优的配合或可帮助有效控制软骨细胞中基因所编码的蛋白的水平,因此软骨产生的量或可完全由机体来完成。更有意思的是,Sox9结合作用的工作模式在不同起源的软骨中是类似的,即从鼻子到肋骨都是相似的。


    研究者McMahon最后说,Sox9对于全身骨骼的正常发育非常重要,当机体中Sox9发生突变时就会发生灾难性的机体病变,比如骨头弯曲以及躯干发育异常等;后期研究者还将通过更深层次的研究来揭示如何利用Sox9来开发治疗相关疾病的新型个体化疗法。


    原文链接:Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian Chondrocyte


    原文摘要:Sox9 encodes an essential transcriptional regulator of chondrocyte specification and differentiation. When Sox9 nuclear activity was compared with markers of chromatin organization and transcriptional activity in primary chondrocytes, we identified two distinct categories of target association. Class I sites cluster around the transcriptional start sites of highly expressed genes with no chondrocyte-specific signature. Here, Sox9 association reflects protein-protein association with basal transcriptional components. Class II sites highlight evolutionarily conserved active enhancers that direct chondrocyte-related gene activity through the direct binding of Sox9 dimer complexes to DNA. Sox9 binds through sites with sub-optimal binding affinity; the number and grouping of enhancers into super-enhancer clusters likely determines the levels of target gene expression. Interestingly, comparison of Sox9 action in distinct chondrocyte lineages points to similar regulatory strategies. In addition to providing insights into Sox family action, our comprehensive identification of the chondrocyte regulatory genome will facilitate the study of skeletal development and human disease.

 

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