Regulation of Salivary Glands-Specific Cystatin S

唾液腺特异性胱抑素 S 的调节

基本信息

项目摘要

DESCRIPTION: Our long-term goal is to understand regulation of tissue specific transcription during salivary gland development using the cystatin S gene as the paradigm. We previously showed this gene to be unique in that it is cell type- and salivary gland-specific, is regulated by hormones and by the autonomic nervous system, and is expressed at a specific stage of postnatal development. Furthermore, cystatin S gene expression, though turned off in adult rats, can be induced by b-receptor mediated mechanisms. Phylogenetic "footprinting" of the cystatin S gene reveals that are at least 3 types of DNA binding "modules" located in the 1.9 kilobase (kb) 5'-flanking sequence, including a hormone module (Fig. 23). Within the hormone module, three putative "domains" have been identified that are found in the 5'-flanking sequence of all known salivary gland-specific genes that have been sequenced. In the cystatin S gene these "domains", I, II and III, include a (GT)27 region located between sequence elements II and III. In addition, a novel GR/PR (glucocorticoid/progesterone, Cys GRE) responsive element, harboring within it an Hmx3 (homeobox) binding site and an estrogen responsive element (ERE) is located between elements I and II. The promoter region of the cystatin S gene also contains a potential CREB/AP-1 binding site, and two other potential glucocorticoid responsive elements (GRDs). To determine which of the cis-elements are functional and responsible for tissue specific regulation of the cystatin S gene, we generated two transgenic mouse models. One expresses 1.9 kb of the 5'-flanking region of the cystatin S gene, upstream of the green fluorescent protein (GFP) reporter gene and contains all of the transcription factor binding "modules, "domains" I, II, and III, and GREs, Hmx3 binding site, CRE/AP-1 and ERE and other cis-acting elements, and the second expressing transgene with 1 kb of the 5'-flanking region contains 3 modules including the "hormone module" (domains I, II, and III, a GRE, Hmx3 binding site, and an ERE) and other cis-acting elements. In conjunction with studies in cell culture, these two models and the additional transgenic mice we propose to generate, will increase our understanding of the cis-acting the additional transgenic mice we propose to generate, will increase our understanding of the cis-acting elements, and transcription factors that determine the salivary gland-specific and developmentally regulated expression of the cystatin S gene. Our two Specific Aims are to:1) identify cis-acting DNA elements that are important for tissue-specific expression and developmental regulation of the cystatin S gene, and 2) identify and characterize trans-acting factors regulating tissue-specific expression and developmental regulation of the cystatin S gene.
描述:我们的长期目标是以胱抑素 S 基因为范例,了解唾液腺发育过程中组织特异性转录的调控。我们之前表明该基因的独特之处在于它是细胞类型和唾液腺特异性的,受激素和自主神经系统调节,并在出生后发育的特定阶段表达。此外,胱抑素 S 基因表达虽然在成年大鼠中被关闭,但可以通过 b 受体介导的机制诱导。半胱氨酸蛋白酶抑制剂 S 基因的系统发育“足迹”揭示了至少 3 种类型的 DNA 结合“模块”位于 1.9 千碱基 (kb) 5'-侧翼序列中,包括激素模块(图 23)。在激素模块内,已鉴定出三个假定的“结构域”,这些结构域存在于已测序的所有已知唾液腺特异性基因的 5' 侧翼序列中。在半胱氨酸蛋白酶抑制剂S基因中,这些“结构域”I、II和III包括位于序列元件II和III之间的(GT)27区域。此外,一种新的 GR/PR(糖皮质激素/黄体酮,Cys GRE)响应元件,其内部包含 Hmx3(同源盒)结合位点,并且雌激素响应元件(ERE)位于元件 I 和 II 之间。半胱氨酸蛋白酶抑制剂 S 基因的启动子区域还包含一个潜在的 CREB/AP-1 结合位点和另外两个潜在的糖皮质激素反应元件 (GRD)。为了确定哪些顺式元件具有功能并负责半胱氨酸蛋白酶抑制剂 S 基因的组织特异性调节,我们生成了两种转基因小鼠模型。一个表达半胱氨酸蛋白酶抑制剂 S 基因 5' 侧翼区域的 1.9 kb,位于绿色荧光蛋白 (GFP) 报告基因的上游,并包含所有转录因子结合“模块”、“结构域”I、II 和 III、GRE、Hmx3 结合位点、CRE/AP-1 和 ERE 以及其他顺式作用元件,第二个表达转基因具有 1 kb 5'-侧翼区域包含 3 个模块,包括“激素模块”(结构域 I、II 和 III、GRE、Hmx3 结合位点和 ERE)和其他顺式作用元件。结合细胞培养的研究,这两种模型和我们建议产生的额外转基因小鼠,将增加我们对顺式作用的理解。我们建议产生的额外转基因小鼠,将增加我们对顺式作用的理解。 了解决定唾液腺特异性和发育调节的胱抑素 S 基因表达的顺式作用元件和转录因子。我们的两个具体目标是:1) 鉴定对半胱氨酸蛋白酶抑制剂 S 基因的组织特异性表达和发育调节非常重要的顺式作用 DNA 元件,2) 鉴定和表征调节组织特异性表达和半胱氨酸蛋白酶抑制剂 S 基因发育调节的反式作用因子。 胱抑素S基因。

项目成果

期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Homeobox protein, Hmx3, in postnatally developing rat submandibular glands.
出生后发育的大鼠颌下腺中的同源框蛋白 Hmx3。
Autonomic regulation of cystatin S gene expression in rat submandibular glands.
大鼠颌下腺胱抑素 S 基因表达的自主调节。
Proto-oncogene fos (c-fos) expression in the heart.
  • DOI:
  • 发表时间:
    1987
  • 期刊:
  • 影响因子:
    8
  • 作者:
    T. Barka;H. vanderNoen;Shaw Pa
  • 通讯作者:
    T. Barka;H. vanderNoen;Shaw Pa
Cloning and sequencing of cDNA encoding a rat salivary cysteine proteinase inhibitor inducible by beta-adrenergic agonists.
编码由 β-肾上腺素能激动剂诱导的大鼠唾液半胱氨酸蛋白酶抑制剂的 cDNA 的克隆和测序。
Sympathetic and parasympathetic regulation of cystatin S gene expression.
半胱氨酸蛋白酶抑制剂 S 基因表达的交感神经和副交感神经调节。
  • DOI:
    10.1016/s0024-3205(01)01379-0
  • 发表时间:
    2001
  • 期刊:
  • 影响因子:
    6.1
  • 作者:
    Shaw,PA;Yu,WH
  • 通讯作者:
    Yu,WH
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PHYLLIS Ann SHAW其他文献

PHYLLIS Ann SHAW的其他文献

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{{ truncateString('PHYLLIS Ann SHAW', 18)}}的其他基金

Controlled expression of a cystatin C-peptide as therapy for Alzheimer's disease
半胱氨酸蛋白酶抑制剂 C 肽的受控表达作为阿尔茨海默病的治疗方法
  • 批准号:
    8190713
  • 财政年份:
    2011
  • 资助金额:
    $ 35.76万
  • 项目类别:
Controlled expression of a cystatin C-peptide as therapy for Alzheimer's disease
半胱氨酸蛋白酶抑制剂 C 肽的受控表达作为阿尔茨海默病的治疗方法
  • 批准号:
    8323235
  • 财政年份:
    2011
  • 资助金额:
    $ 35.76万
  • 项目类别:
RIBOZYME MEDIATED KNOCKOUT OF THE CYSTATIN S GENE
核酶介导的胱抑素 S 基因敲除
  • 批准号:
    2132565
  • 财政年份:
    1995
  • 资助金额:
    $ 35.76万
  • 项目类别:
RIBOZYME MEDIATED KNOCKOUT OF THE CYSTATIN S GENE
核酶介导的胱抑素 S 基因敲除
  • 批准号:
    2132566
  • 财政年份:
    1995
  • 资助金额:
    $ 35.76万
  • 项目类别:
AGE-RELATED RESPONSE OF SALIVARY GLANDS TO ISOPROTERENOL
唾液腺对异丙肾上腺素的年龄相关反应
  • 批准号:
    3221952
  • 财政年份:
    1987
  • 资助金额:
    $ 35.76万
  • 项目类别:
REGULATION OF CYSTATIN S GENE EXPRESSION
胱抑素S基因表达的调控
  • 批准号:
    6379637
  • 财政年份:
    1987
  • 资助金额:
    $ 35.76万
  • 项目类别:
AGE RELATED RESPONSE OF SALIVARY GLANDS TO ISOPROTERENOL
唾液腺对异丙肾上腺素的年龄相关反应
  • 批准号:
    2129978
  • 财政年份:
    1987
  • 资助金额:
    $ 35.76万
  • 项目类别:
AGE RELATED RESPONSE OF SALIVARY GLANDS TO ISOPROTERENOL
唾液腺对异丙肾上腺素的年龄相关反应
  • 批准号:
    2129979
  • 财政年份:
    1987
  • 资助金额:
    $ 35.76万
  • 项目类别:
Regulation of Salivary Glands-Specific Cystatin S
唾液腺特异性胱抑素 S 的调节
  • 批准号:
    6922028
  • 财政年份:
    1987
  • 资助金额:
    $ 35.76万
  • 项目类别:
Regulation of Salivary Glands-Specific Cystatin S
唾液腺特异性胱抑素 S 的调节
  • 批准号:
    6823909
  • 财政年份:
    1987
  • 资助金额:
    $ 35.76万
  • 项目类别:

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SAA1基因5侧翼区多态性对SAA1转录活性的影响
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