CELL-SPEC TRANS MECH CONTROLLING TYPE I COLLAGEN GENES

细胞规格跨机械控制 I 型胶原蛋白基因

基本信息

批准号：
6389076
负责人：
Benoit de Crombrugghe
金额：
$ 39.23万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-07-01 至 2003-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6389076
关键词：
Xenopus oocyte cell differentiation collagen complementary DNA fibroblasts gene induction /repression genetic enhancer element genetically modified animals laboratory mouse oligonucleotides osteoblasts osteosarcoma tissue /cell culture

项目摘要

DESCRIPTION: The hypothesis behind this application is that type I collagen genes are activated during embryonic development in a discrete number of cell types by some of the same transcriptional mechanisms which also control the differentiated phenotypes of these cells. The objective of the proposal is to elucidate the mechanisms that control expression of these genes in fibroblasts and osteoblasts and, consequently, broader genetic programs in these cell types. Previous work has indicated that separate cis-acting elements in the type I collagen genes control expression of reporter genes in different type I collagen producing cells. One of these elements in the mouse proa1(I) gene controls osteoblast expression; another one is a potent far-upstream enhancer in the proa2(I) gene which controls expression mainly in fibroblasts. This application is divided into two parts. One proposes to delineate the minimal elements in the proa2(I) far-upstream enhancer which control expression of a reporter gene in fibroblastic cells of transgenic mice. It is expected that this minimal segment can then be used to identify fibroblast-specific or fibroblast-enriched DNA binding transcription factors which can activate the fibroblast elements in the proa2(I) gene. Subsequently, cDNAs for these DNA binding proteins will be cloned and characterized. The second part of the project will further define the DNA sequence in the proa1(I) gene critical for osteoblast expression in transgenic mice. It is expected that this sequence can be used to identify osteoblast-specific or osteoblast-enriched DNA binding proteins which control expression of the proa1(I) gene in osteoblasts. Also in this case, cDNAs for these polypeptides will then be cloned and characterized. Together, these two studies will enhance our understanding of the molecular determinants underlying the differentiation of mesenchymal cell precursors.

描述：此应用程序背后的假设是I型胶原蛋白在胚胎发育过程中激活基因以离散数量的数量通过某些相同的转录机制，细胞类型也可以控制这些细胞的分化表型。提案的目的是为了阐明控制这些基因在成纤维细胞和成骨细胞，因此，更广泛的遗传程序这些细胞类型。以前的工作表明单独的顺式作用 I型胶原基因控制报告基因的表达的元素在不同的I型胶原蛋白产生细胞中。这些元素之一小鼠ProA1（i）基因控制成骨细胞表达；另一个是有效的 ProA2（i）基因中的遥远增强子，主要控制表达在成纤维细胞中。该应用程序分为两个部分。一个提议描绘proA2（i）远面增强器中的最小元素哪个控制报告基因在成纤维细胞中的表达转基因小鼠。预计可以使用该最小段鉴定成纤维细胞特异性或成纤维细胞富集的DNA结合可以激活成纤维细胞元素的转录因子 proa2（i）基因。随后，这些DNA结合蛋白的cDNA将是克隆和特征。项目的第二部分将进一步定义proA1（i）基因中至关重要的成骨细胞的DNA序列转基因小鼠的表达。预计这个序列可以是用于识别成骨细胞特异性或成骨细胞富集的DNA结合控制成骨细胞中proA1（i）基因表达的蛋白质。还在这种情况下，这些多肽的cDNA然后将被克隆，并特征。这两项研究一起将增强我们的理解间质分化的基础分子决定因素细胞前体。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Two different negative and one positive regulatory factors interact with a short promoter segment of the alpha 1 (I) collagen gene.

两种不同的负调节因子和一种正调节因子与 α 1 (I) 胶原蛋白基因的短启动子片段相互作用。

DOI：
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
0
作者：
Karsenty,G;deCrombrugghe,B
通讯作者：
deCrombrugghe,B

Tissue-specific expression of the mouse alpha 2(I) collagen promoter. Studies in transgenic mice and in tissue culture cells.

小鼠 α 2(I) 胶原蛋白启动子的组织特异性表达。

DOI：
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
0
作者：
Goldberg,H;Helaakoski,T;Garrett,LA;Karsenty,G;Pellegrino,A;Lozano,G;Maity,S;deCrombrugghe,B
通讯作者：
deCrombrugghe,B

Evidence for three major transcription activation elements in the proximal mouse proalpha2(I) collagen promoter.

近端小鼠 proalpha2(I) 胶原蛋白启动子中三个主要转录激活元件的证据。