Function and mechanism of TGIF1 in erythroid differentiation
LIU Shu-ge 1,2, ZHENG Jia-wen 1,2, LI Yan-ming 1,2, ZHANG Zhao-jun 1,3, FANG Xiang-dong 1,2
1.Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; 2. College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; 3. Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100190, China
Abstract: Objective To identify the potential regulator which can promote erythroid differentiation and to validate its function, and to discuss the mechanism of erythroid differentiation. Methods High-throughout RNA-seq data of erythroid cells at different differentiation stages was analyzed to screen potential erythroid transcriptional regulatory factor. Expression of candidate factor was interfered in TF-1 cells to investigate its role in erythroid differentiation. Transcriptome analyses of candidate knockdown TF-1 cells and bioinformatics techniques were performed to correlated erythroid genes and signaling pathways. ResultsTGIF1 was determined as a potential erythroid transcription factor as its consistent expression along with erythroid differentiation. In the TGIF1 -knockdown TF-1 cells, the mRNA expression of ε-globin,γ-globin, erythroid-specific transcription factors such as GATA1 and KLF1 , and erythroid-specific cell surface marker such as CD235a were all lower than that in control cells; and so was the hemoglobin concentration. In TGIF1-overexpressed TF-1 cells, the mRNA expression of γ-globin is higher than that in control cells. After three days of induction by erythropoietin, CD235a expression on the surface of TGIF1 -overexpressed cells was higher than that of control cells. The transcriptome analyses of TGIF1-knockdown TF-1 cells revealed that the expression of Smad family genes was up-regulated and GATA1 and ALAS2 were two most significant down-regulated genes. ConclusionTGIF1 is an erythroid transcription factor which can promote erythroid differentiation probably by its interference with the expression of Smad family genes or two erythroid genes GATA1andALAS2.
2016, Vol. 4 
