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.
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Article Synopsis
- The Krüppel-like transcription factors (KLF) are important zinc finger proteins that play a role in activating and suppressing gene transcription, impacting various developmental processes.
- A comprehensive analysis of the chicken KLF gene family reveals fourteen identified KLF genes, including the confirmation that KLF1 is the true ortholog of KLF17 in other species.
- Expression studies show that KLFs 3, 7, 8, and 9 are widely expressed during embryonic development, while other KLFs like 2, 4, 5, 6, 10, 11, 15, and 17 have more restricted roles, indicating their specific functions in early development.
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