Erythroid Kruppel-like factor directly activates the basic Kruppel-like factor gene in erythroid cells
Erythroid Kruppel-like factor directly activates the basic Kruppel-like factor gene in erythroid cells
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DOI：
10.1128/mcb.01658-06
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发表时间：
2007-04-01
影响因子：
5.3
通讯作者：
Crossley, Merlin
中科院分区：
文献类型：
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作者：
Funnell, Alister P. W.;Maloney, Christopher A.;Crossley, Merlin
Sp/Kriippel 样因子 (Sp/KIf) 家族由约 25 个锌指转录因子组成，可识别 CACCC 盒和富含 GC 的元件。我们研究了基本 Kruppel 样因子 (Bklf/Klf3)，并表明在红系组织中其表达高度依赖于另一个家族成员，红系 Kruppel 样因子 (Eklf/Kif1)。我们观察到 Eklf 缺失小鼠胚胎的红系组织中 Bklf mRNA 显着减少。我们发现 Bklf 主要由两个启动子驱动，一个普遍活跃的富含 GC 的上游启动子 la 和一个红系下游启动子 1b。两个启动子的转录物编码相同的蛋白质。有趣的是，在红系细胞中，普遍存在的启动子和红系启动子都依赖于 Eklf。 Eklf 还在瞬时测定中激活两个启动子。利用诱导型 Eklf 的实验证明，在蛋白质合成抑制剂存在的情况下，内源 Bklf 基因会被激活。激活动力学也与 Bklf 是 Eklf 的直接目标一致。染色质免疫沉淀测定证实 Eklf 与两个 Bklf 启动子相关。 Eklf 通常是转录激活因子，而 Bklf 则被认为是转录抑制因子。我们的结果支持反馈交叉调节发生在体内 Sp/Klf 家族内的假设。
The Sp/Kriippel-like factor (Sp/KIf) family is comprised of around 25 zinc finger transcription factors that recognize CACCC boxes and GC-rich elements. We have investigated basic Kruppel-like factor (Bklf/Klf3) and show that in erythroid tissues its expression is highly dependent on another family member, erythroid Kruppel-like factor (Eklf/Kif1). We observe that Bklf mRNA is significantly reduced in erythroid tissues from Eklf-null murine embryos. We find that Bklf is driven primarily by two promoters, a ubiquitously active GC-rich upstream promoter, la, and an erythroid downstream promoter, 1b. Transcripts from the two promoters encode identical proteins. Interestingly, both the ubiquitous and the erythroid promoter are dependent on Eklf in erythroid cells. Eklf also activates both promoters in transient assays. Experiments utilizing an inducible form of Eklf demonstrate activation of the endogenous Bklf gene in the presence of an inhibitor of protein synthesis. The kinetics of activation are also consistent with Bklf being a direct Eklf target. Chromatin immunoprecipitation assays confirm that Eklf associates with both Bklf promoters. Eklf is typically an activator of transcription, whereas Bklf is noted as a repressor. Our results support the hypothesis that feedback cross-regulation occurs within the Sp/Klf family in vivo.