Synergistic activation of the rat laminin γ1 chain promoter by the gut-enriched Kruppel-like factor (GKLF/KLF4) and Sp1
Synergistic activation of the rat laminin γ1 chain promoter by the gut-enriched Kruppel-like factor (GKLF/KLF4) and Sp1
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DOI：
10.1093/nar/30.11.2270
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发表时间：
2002-06-01
影响因子：
14.9
通讯作者：
Bomsztyk, K
中科院分区：
文献类型：
--
作者：
Higaki, Y;Schullery, D;Bomsztyk, K
层粘连蛋白是一种存在于细胞外基质中的多功能异三聚体蛋白，它调节包括细胞分化在内的组织结构过程。层粘连蛋白γ - 1是最广泛表达的层粘连蛋白链，其缺失导致小鼠胚胎早期死亡。层粘连蛋白γ -1链基因（LAMC1）启动子含有多个富含GC/ gt的基序，包括bcn-1元件。在酵母单杂交筛选中，以bcn1元素为诱饵，从大鼠系膜细胞文库中克隆出富含肠道的kklpel样因子（GKLF或KLF4）。我们发现GKLF结合bcn-1，但这种结合不是GKLF介导的LAMC1启动子激活所必需的。GKLF的活性依赖于与另一个kruppel样因子Sp1的协同作用。LAMC1启动子似乎具有多个GKLF-和sp1响应元件，这可能解释了协同激活。我们提供的证据表明，GKLF和Sp1的协同作用取决于启动子背景和GKLF激活和dna结合域的完整性。GKLF被认为参与了细胞从增殖到分化的转变。因此，当需要层粘连蛋白调节细胞分化时，Sp1-GKLF对LAMC1启动子的协同激活可能是层粘连蛋白γ - 1链表达的途径之一。
Laminin is a multifunctional heterotrimeric protein present in extracellular matrix where it regulates processes that compose tissue architecture including cell differentiation. Laminin gamma1 is the most widely expressed laminin chain and its absence causes early lethality in mouse embryos. Laminin gamma1 chain gene (LAMC1) promoter contains several GC/GT-rich motifs including the bcn-1 element. Using the bcn-1 element as a bait in the yeast one-hybrid screen, we cloned the gut-enriched Kruppel-like factor (GKLF or KLF4) from a rat mesangial cell library. We show that GKLF binds bcn-1, but this binding is not required for the GKLF-mediated activation of the LAMC1 promoter. The activity of GKLF is dependent on a synergism with another Kruppel-like factor, Sp1. The LAMC1 promoter appears to have multiple GKLF- and Sp1-responsive elements which may account for the synergistic activation. We provide evidence that the synergistic action of GKLF and Sp1 is dependent on the promoter context and the integrity of GKLF activation and DNA-binding domain. GKLF is thought to participate in the switch from cell proliferation to differentiation. Thus, the Sp1-GKLF synergistic activation of the LAMC1 promoter may be one of the avenues for expression of laminin gamma1 chain when laminin is needed to regulate cell differentiation.