A Transcription Activator with Restricted Tissue Distribution Regulates Cell-specific Expression of α1(XI) Collagen*

A Transcription Activator with Restricted Tissue Distribution Regulates Cell-specific Expression of α1(XI) Collagen*
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组织分布受限的转录激活剂调节 α1(XI) 胶原蛋白的细胞特异性表达*

DOI:
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发表时间:
1997
影响因子:
4.8
通讯作者:
F. Ramirez
F. Ramirez
中科院分区:
生物学2区
文献类型:
--
作者:
A. Kinoshita;P. Greenwel;Shoichiro Tanaka;M. Di Liberto;H. Yoshioka;F. Ramirez

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不同的调控程序可能控制α1(XI)胶原(COL11A1)基因在软骨和非软骨组织中的表达,并与不同的胶原基因协同作用。在这里,我们报告了近端COL11A1启动子的结构性和组织特异性活性所需的Acis作用元件的鉴定。该元件结合了一种显然是新的激活物,其表达主要限制在间充质来源的细胞上,但不是唯一的。用野生型和突变型构建物进行的瞬时转染实验证明了45碱基对的上游元件(Fp9)对启动子活性的关键贡献。相同的功能测试和DNA结合分析将FP9的关键部分缩小到一个20个碱基对的序列,该序列由一个与GATA共识基序具有很强同源性的不完美回文组成。尽管在体外能够与GATA蛋白结合,但Fp9实际上是由一个独特的∼100 kDa多肽(Fp9C)识别的,该多肽可能属于锌指转录因子家族。FP9C结合主要见于间充质来源的细胞核,包括那些活跃参与COL11A1转录的细胞。Fp9C结合水平与体外细胞分化程度呈正相关。因此,fp9C代表了组织特异性和分化相关的转录因子的一个不寻常的例子,在硬结缔组织和软结缔组织中重叠表达。
Different regulatory programs are likely to control expression of the α1(XI) collagen (COL11A1) gene in cartilaginous and non-cartilaginous tissues and in coordination with different collagen genes. Here, we report the identification of acis-acting element that is required for constitutive and tissue-specific activity of the proximal COL11A1 promoter. The element binds an apparently novel activator whose expression is restricted mostly, but not exclusively, to cells of mesenchymal origin. Transient transfection experiments using wild-type and mutant constructs demonstrated the critical contribution of a 45-base pair upstream element (FP9) to promoter activity. The same functional tests and DNA binding assays narrowed down the critical portion of FP9 to a 20-base pair sequence, which consists of an imperfect palindrome with strong homology to the GATA consensus motif. Despite being able to bind GATA proteins in vitro, FP9 is actually recognized by a distinct ∼100-kDa polypeptide (FP9C) probably belonging to the zinc-finger family of transcription factors. FP9C binding was mostly identified in nuclei from cells of mesenchymal origin, including those actively engaged in COL11A1 transcription. A positive correlation was also established between the level of FP9C binding and the degree of cell differentiation in vitro. Thus, FP9C represents an unusual example of tissue-specific and differentiation-related transcription factor with overlapping expression in hard and soft connective tissues.
DOI: 10.1016/s0021-9258(19)38305-x
发表时间: 1990-08
期刊: The Journal of biological chemistry
影响因子: --
作者:
S. Boast;M. Su;F. Ramirez;M. Sánchez;E. Avvedimento
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DOI: --
发表时间: 1992-08
期刊: Development
影响因子: 4.6
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通讯作者: P. Cserjesi;Brenda Lilly;Laura Bryson;Yaoqi Wang;David Sassoon;E. N. Olson
鉴定对 pro-alpha 2(V) 胶原蛋白基因 (COL5A2) 的细胞类型特异性转录所必需的上游调控区域。
DOI: --
发表时间: 1992
期刊: The Journal of biological chemistry
影响因子: --
作者:
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通讯作者: Ramirez,F
DOI: 10.1006/dbio.1996.0165
发表时间: 1996-07-10
影响因子: 2.7
作者:
Morrisey, EE;Ip, HS;Parmacek, MS
通讯作者: Parmacek, MS
DOI: 10.1002/ajmg.1320450203
发表时间: 1993-01-15
期刊: AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子: --
作者:
SLACK, JL;LISKA, DJ;BORNSTEIN, P
通讯作者: BORNSTEIN, P