KLFs对珠蛋白基因表达和红系分化的调控作用

Krüppel样因子(Krüppel-like factors, KLFs)是一组与真核基因转录调控密切相关的锌指蛋白.KLFs高度保守的羧基末端含3个串联的Cys2His2型锌指结构,用于结合GC盒和CACCC盒等DNA序列. 红细胞中特异表达的珠蛋白基因和许多红系调控因子中都含有CACCC盒.已有研究发现,多个KLFs通过结合CACCC盒参与调控珠蛋白基因表达和红系分化,例如,KLF1通过结合β-珠蛋白启动子和位点控制区(locus control region, LCR),促进β-珠蛋白的表达、γ-向β-珠蛋白基因的转换和红系分化;KLF2、KLF11和KLF13分别促进ε-和γ-珠蛋白基因的表达;KLF4促进α-和γ-珠蛋白基因的表达;KLF3和KLF8则抑制ε-和γ-珠蛋白基因的表达. 本文综述了KLFs调控珠蛋白基因表达和红系分化的研究进展.     

KLF转录因子家族与脂肪细胞分化

Kruppel样转录因子（Kruppel-like factors, KLF）是一类具有锌指结构的转录因子,其典型结构特征是在其羧基端具有3个C2H2锌指结构. KLF广泛参与细胞增殖、凋亡、分化以及胚胎发育等多个生命活动的调控. 近年来脂肪细胞分化研究的结果显示,KLF家族的多个成员参与脂肪细胞分化过程的调控,既有促进脂肪细胞分化的,也有抑制脂肪细胞分化的. 其中KLF4通过与Krox20协同作用,激活C/EBPβ（CCAAT-enhancer-binding protein β）基因表达,促进脂肪细胞分化;KLF5和 KLF15都通过直接结合到氧化物酶增殖体激活受体γ（peroxisome proliferator-activated receptor γ, PPARγ）基因的启动子,激活PPARγ基因表达,促进脂肪细胞分化;而KLF6则通过抑制前脂肪细胞因子（pre-adipocyte factor 1, PREF1）基因表达,促进脂肪细胞分化. 抑制脂肪细胞分化的KLF2通过结合于PPARγ的启动子,抑制PPARγ基因表达,从而抑制脂肪细胞的分化;KLF3通过募集辅助抑制因子C-末端结合蛋白（c-terminal binding protein, CtBP）形成KLF3 CtBP抑制复合体,结合于C/EBPα（CCAAT-enhancer-binding protein α）基因的启动子,抑制C/EBPα表达,进而抑制脂肪细胞的分化;KLF7通过抑制葡萄糖转运蛋白2（glucose transporter2,GLUT2）基因的表达抑制脂肪细胞的成熟. 本文综述这些KLF转录因子在脂肪细胞分化过程的作用及其作用的机制.     

Krüppel样因子在肌肉组织中的功能研究进展

Krüppel样因子(Krüppel-like factors, KLFs)是一类C-末端含有3个C₂H₂锌指结构的转录因子,N-末端为转录调控结构域,能够结合多种特异蛋白质,介导转录调控。目前在人体基因组中共发现18种KLFs,它们在多种类型人类细胞的分化、表型维持和生理功能调控中发挥重要作用。多个KLFs参与了对人和动物的心肌、平滑肌和骨骼肌的发育和功能的调控。在心肌中,KLF4、KLF10、KLF11和KLF15参与心肌肥大的负调控,KLF6参与调控心脏纤维化,KLF13调控胚胎时期的心肌发育。在血管平滑肌中,KLF4受促增殖或促分化因子调控,介导调控血管平滑肌表型转换;KLF5促进血管平滑肌增殖,KLF8和KLF15抑制血管平滑肌增殖。在骨骼肌中,KLF2、KLF3、KLF4、KLF10和KLF15调控骨骼肌发育,此外,KLF15是肌肉组织能量代谢的调节因子。本文综述了KLFs在心肌、平滑肌和骨骼肌中的功能研究进展,为进一步揭示KLFs在肌肉组织中的作用和肌肉相关疾病的分子机制提供参考。     

Krüppel样转录因子8(KLF8)的结构及功能

Krüppel样转录因子8(Krüppel-like factor 8,KLF8)是KLFs家族中的一员.KLF8在羧基端含有3个保守的C2H2锌指结构域,用于与DNA结合.KLF8的转录受粘着斑激酶(focal adhesion kinase,FAK)、KLF1(erythroid krüppel-like fact...     

IP(3)-dependent intracellular Ca(2+) release is required for cAMP-induced c-fos expression in hippocampal neurons

Endothelial argininosuccinate synthetase 1 (ASS1) regulates the provision of l-arginine to nitric oxide synthase 3 (NOS3). Previous studies demonstrated that endothelial ASS1 expression was induced by laminar shear stress (LSS) and that this enzyme plays a role in maintaining anti-inflammatory microenvironments through enhancing NO production. However, differently from the case of NOS3, the regulatory mechanism for the endothelial ASS1 expression in response to LSS is not well understood. This study addressed a specific issue whether endothelial ASS1 expression is regulated by Kruppel-like factors (KLFs) that are presumed to coordinate endothelial gene expressions in response to LSS. The cDNA microarray data indicated that LSS stimulated the expression of numerous KLFs in human umbilical vein endothelial cells. KLF4 showed the highest fold increase and LSS-dependent increases of KLF4 and most other KLFs were similar in young versus senescent endothelial cells. LSS-induced KLF4 expression was verified by RT-PCR and Western blotting. LSS-induced ASS1 expression and NO production were suppressed by a small interfering RNA for KLF4. The ectopic expression of KLF4 led to the increase of ASS1 expression and NO production. The present study demonstrated a key regulatory role of KLF4 in the endothelial ASS1 expression and NO production in response to LSS.     

Evolutionary conservation of KLF transcription factors and functional conservation of human gamma-globin gene regulation in chicken

The Krüppel-like factors (KLFs) are a family of Cys2His2 zinc-finger DNA binding proteins with homology to Drosophila Krüppel. KLFs can bind to CACCC elements, which are important in controlling developmental programs. The CACCC promoter element is critical for the developmental regulation of the human gamma-globin gene. In the present study, chicken homologues of the human KLF2, 3, 4, 5, 9, 11, 12, 13, and 15 genes were identified. Phylogenetic analysis confirms that these genes are more closely related to their human homologues than they are to other chicken KLFs. This work also represents the first systematic study of the expression patterns of KLFs during erythroid development. In addition, transient transfections of human globin constructs into 5-day (primitive) chicken red blood cells show that human gamma-globin expression is regulated via its CACCC promoter element. This indicates that a CACCC-binding factor(s) important for gamma-globin expression functions in 5-day chicken red cells.