Identification of SCAN domain zinc-finger gene ZNF449 as a novel factor of chondrogenesis.
Identification of SCAN domain zinc-finger gene ZNF449 as a novel factor of chondrogenesis.
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DOI：
10.1371/journal.pone.0115169
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Saito T
中科院分区：
文献类型：
--
作者：
Okada K;Fukai A;Mori D;Hosaka Y;Yano F;Chung UI;Kawaguchi H;Tanaka S;Ikeda T;Saito T
转录因子SOX9、SOX5和SOX6是软骨细胞发生和分化所必需的。然而，诱导SOX基因的分子机制却知之甚少。为了解决这一问题，我们先前通过5‘RACE分析确定了SOX6的人类胚胎增强子，并确定了46bp的核心增强子区域(CES6)。我们首先以CES6为诱饵，进行酵母单杂交筛选其他软骨形成因子，并鉴定出一个锌指蛋白ZNF449。ZNF449和Zfp449，小鼠的对应基因，反式激活SOX6，SOX9和COL2A1的增强子或启动子。Zfp449在软骨、头盖骨、肌肉和肌腱等间充质组织中表达，在脑、肺、肾等组织中也有表达。在小鼠胚胎四肢软骨中，Zfp449蛋白大量分布于关节周围软骨细胞中，并随着分化程度的增加而逐渐减少。在成年小鼠关节软骨中也检测到Zfp449蛋白。在人骨髓间充质干细胞向软骨方向分化的过程中，ZNF449在分化早期表达上调，其过表达仅在分化初期增强SOX9和SOX6的表达。我们进一步建立了Zfp449基因敲除小鼠，以检验其在体内的作用；然而，在骨骼发育和关节软骨内稳态方面没有观察到明显的异常。ZNF449可能调节间充质祖细胞向软骨细胞分化，但其机制尚不清楚。
Transcription factors SOX9, SOX5 and SOX6 are indispensable for generation and differentiation of chondrocytes. However, molecular mechanisms to induce the SOX genes are poorly understood. To address this issue, we previously determined the human embryonic enhancer of SOX6 by 5′RACE analysis, and identified the 46-bp core enhancer region (CES6). We initially performed yeast one-hybrid assay for screening other chondrogenic factors using CES6 as bait, and identified a zinc finger protein ZNF449. ZNF449 and Zfp449, a counterpart in mouse, transactivated enhancers or promoters of SOX6, SOX9 and COL2A1. Zfp449 was expressed in mesenchyme-derived tissues including cartilage, calvaria, muscle and tendon, as well as in other tissues including brain, lung and kidney. In limb cartilage of mouse embryo, Zfp449 protein was abundantly located in periarticular chondrocytes, and decreased in accordance with the differentiation. Zfp449 protein was also detected in articular cartilage of an adult mouse. During chondrogenic differentiation of human mesenchymal stem cells, ZNF449 was increased at an early stage, and its overexpression enhanced SOX9 and SOX6 only at the initial stage of the differentiation. We further generated Zfp449 knockout mice to examine the in vivo roles; however, no obvious abnormality was observed in skeletal development or articular cartilage homeostasis. ZNF449 may regulate chondrogenic differentiation from mesenchymal progenitor cells, although the underlying mechanisms are still unknown.
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DOI：
10.1006/bbrc.2001.5777
发表时间：
2001-10-26
影响因子：
3.1
作者：
Tsutsumi, S;Shimazu, A;Kato, Y
通讯作者：
Kato, Y
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
作者：
Lefebvre, V;Huang, WD;deCrombrugghe, B
通讯作者：
deCrombrugghe, B
影响因子：
4.8
作者：
Sekiya, I;Tsuji, K;Noda, M
通讯作者：
Noda, M