A network of Kruppel-like factors (klfs) -: Klf8 is repressed by Klf3 and activated by Klf1 in vivo
A network of Kruppel-like factors (klfs) -: Klf8 is repressed by Klf3 and activated by Klf1 in vivo
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DOI：
10.1074/jbc.m804831200
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发表时间：
2008-10-03
影响因子：
4.8
通讯作者：
Crossley, Merlin
中科院分区：
文献类型：
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作者：
Eaton, Sally A.;Funnell, Alister P. W.;Crossley, Merlin
Sp/KLF(Kruppel-like factors)家族的转录因子调控造血、脂肪生成和干细胞维持等生物学过程。在此，我们发现BKLF或KLF3(碱性Kruppel-like factor8)在体内抑制KLF8(Kruppel-like factor8)基因。相反，EKLF或KLF1(红系Kruppel样因子)激活KLF8基因。KLF8由两个启动子驱动，两个启动子都含有多个CACCC位点。KLF3可以抑制KLF1介导的两个启动子的激活。染色质免疫沉淀实验证实KLF3在体内占据了两个KLF8启动子。有趣的是，在KLF3基因敲除组织中，KLF1获得通道，结合并激活两个KLF8启动子。这些结果证明了体内激活和抑制KLF之间的直接竞争。再加上之前有证据表明KLF1直接激活了KLF3基因，这些结果揭示了KLF家族内部复杂的串扰网络。对KLF家族成员之间的交叉调节和潜在冗余的认识对于解释各种KLF基因敲除小鼠和在特定背景下理解单个KLF至关重要。
Transcription factors of the Sp/Klf (Kruppel-like factor) family regulate biological processes such as hematopoiesis, adipogenesis, and stem cell maintenance. Here we show that Bklf or Klf3 ( Basic Kruppel-like factor) represses the Klf8 (Kruppel-like Factor 8) gene in vivo. Conversely, Eklf or Klf1 (Erythroid Kruppel-like factor) activates the Klf8 gene. Klf8 is driven by two promoters, both of which contain multiple CACCC sites. Klf3 can repress Klf1-mediated activation of both promoters. Chromatin immunoprecipitation experiments confirm that Klf3 occupies both Klf8 promoters in vivo. Interestingly, in Klf3 knock-out tissue Klf1 gains access, binds, and activates both Klf8 promoters. These results demonstrate direct competition between activating and repressing Klfs in vivo. Together with previous evidence that Klf1 directly activates the Klf3 gene, the results reveal an elaborate network of cross-talk within the Klf family. The recognition of cross-regulation and potential redundancy between Klf family members is critical to the interpretation of various Klf knock-out mice and the understanding of individual Klfs in particular contexts.