Synergistic regulation of the erythroid differentiation of K562 cells by KLF1 and KLF9
Received date: 2018-06-29
Revised date: 2018-09-30
Online published: 2018-10-24
Supported by
Supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010200);the National Natural Science Foundation of China(81700097);the National Natural Science Foundation of China(81700116);the National Natural Science Foundation of China(81670109);the National Natural Science Foundation of China(31471115);the National Natural Science Foundation of China(31371300)
Krüppel-like factors (KLFs) regulate diverse physiological processes such as the differentiation and development of red blood cells. However, it remains unclear whether KLFs exhibit synergistic regulatory effects. Transcriptomic data from our previous study showed that KLF1 and KLF9 expression was significantly higher in differentiated red blood cells than in hematopoietic stem cells. In the present study, we manipulated KLF1 and KLP9 gene expression by overexpressing or knocking down KLF1 and KLF9 in K562 cells and revealed a positive correlation between the expression of KLF1 and KLF9; their co-expression can significantly promote erythroid differentiation and specifically enhance β-globin gene expression. Further, we analyzed the transcriptome data of K562 cells with altered KLF1/KLF9 levels and found that KLF1 and KLF9 synergistically regulated erythroid differentiation through the PI3K-Akt and FoxO signaling pathways. KLF1 and KLF9 may exert this synergistic effect through FOS, TF, and IL8 in K562 cells. We have provided evidence that KLF1 and KLF9 play a synergistic role in regulating erythroid differentiation.
Lan Ren,Rudan Xiao,Qian Zhang,Xiaomin Lou,Zhaojun Zhang,Xiangdong Fang . Synergistic regulation of the erythroid differentiation of K562 cells by KLF1 and KLF9[J]. Hereditas(Beijing), 2018 , 40(11) : 998 -1006 . DOI: 10.16288/j.yczz.18-174
| [1] | Conkright MD, Wani MA, Anderson KP, Lingrel JB . A gene encoding an intestinal-enriched member of the Kruppel- like factor family expressed in intestinal epithelial cells. Nucleic Acids Res, 1999,27(5):1263-1270. | |||
| [2] | Mcconnell BB, Yang VW . Mammalian Krüppel-like factors in health and diseases. Physiol Rev, 2010,90(4):1337-1381. | |||
| [3] | Xiong Q, Ruan XY, Fang XD . Progress on Sp1-like and Krüppel-like factors. Hereditas (Beijing), 2010,32(6):531-538. | |||
| [3] | 熊倩, 阮修艳, 方向东 . Sp1/Krüppel样因子的研究进展. 遗传, 2010,32(6):531-538. | |||
| [4] | Xiong Q, Zhang ZJ, Fang XD . Regulation of KLF on globin expression and erythroid differentiation. Chin J Biochem Mol Biol, 2011,27(8):693-699. | |||
| [4] | 熊倩, 张昭军, 方向东 . KLFs对珠蛋白基因表达和红系分化的调控作用. 中国生物化学与分子生物学报, 2011,27(8):693-699. | |||
| [5] | Zhou D, Liu K, Sun CW, Pawlik KM, Townes TM . KLF1 regulates BCL11A expression and gamma- to beta-globin gene switching. Nat Genet, 2010,42(9):742-744. | |||
| [6] | Tallack MR, Whitington T, Yuen WS, Wainwright EN, Keys JR, Gardiner BB, Nourbakhsh E, Cloonan N, Grimmond SM, Bailey TL, Perkins AC . A global role for KLF1 in erythropoiesis revealed by ChIP-seq in primary erythroid cells. Genome Res, 2010,20(8):1052-1063. | |||
| [7] | Basu P, Morris PE, Haar JL, Wani MA, Lingrel JB, Gaensler KM, Lloyd JA . KLF2 is essential for primitive erythropoiesis and regulates the human and murine embryonic beta-like globin genes in vivo. Blood, 2005,106(7):2566-2571. | |||
| [8] | Asano H, Li X S, Stamatoyannopoulos G . FKLF, a novel krüppel-like factor that activates human embryonic and fetal β-like globin genes. Mol Cell Biol, 1999,19(5):3571. | |||
| [9] | Hu JH, Navas P, Cao H, Stamatoyannopoulos G, Song CZ . Systematic RNAi studies on the role of Sp/KLF factors in globin gene expression and erythroid differentiation. J Mol Biol, 2007,366(4):1064-1073. | |||
| [10] | Funnell AP W, Norton L J, Mak K S, Burdach J, Artuz C M, Twine N A, Wilkins M R, Power C A, Hung T T, Perdomo J . The CACCC-Binding protein KLF3/BKLF represses a subset of KLF1/EKLF target Ggenes and is required for proper erythroid maturation in vivo. Mol Cell Biol, 2012,32(16):3281-3292. | |||
| [11] | van Vliet J, Crofts LA, Quinlan KGR, Czolij R, Perkins AC, Crossley M . Human KLF17 is a new member of the Sp/KLF family of transcription factors. Genomics, 2006,87(4):474-482. | |||
| [12] | Funnell AP, Norton L J, Mak KS, Burdach J, Artuz CM, Twine NA, Wilkins MR, Power CA, Hung TT, Perdomo J, Koh P, Bell-Anderson KS, Orkin SH, Fraser ST, Perkins AC, Pearson RC, Crossley M . The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo. Mol Cell
/
|