RRC ID 45427
著者 Okada K, Fukai A, Mori D, Hosaka Y, Yano F, Chung UI, Kawaguchi H, Tanaka S, Ikeda T, Saito T.
タイトル Identification of SCAN domain zinc-finger gene ZNF449 as a novel factor of chondrogenesis.
ジャーナル PLoS One
Abstract 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.
巻・号 9(12)
ページ e115169
公開日 2014-1-1
DOI 10.1371/journal.pone.0115169
PII PONE-D-14-36555
PMID 25546433
PMC PMC4278888
MeSH Animals Cartilage, Articular / metabolism Cell Line Chondrocytes / cytology Chondrocytes / metabolism Chondrogenesis* DNA-Binding Proteins / chemistry DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Humans Male Mesenchymal Stem Cells / cytology Mesenchymal Stem Cells / metabolism Mice Mice, Inbred C57BL Organ Specificity Protein Structure, Tertiary SOX Transcription Factors / genetics SOX Transcription Factors / metabolism Zinc Fingers
IF 2.74
引用数 3
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 HeLa