TFII-I/GTF2I regulates globin gene expression and stress response in erythroid cells

Transcription factor TFII-I/GTF2I is ubiquitously expressed and has been shown to play a role in the differentiation of hematopoietic cells and in the response to various cellular stressors. We previously demonstrated that TFII-I acts as a repressor of adult β-globin gene transcription and positively regulates the expression of stress response proteins, including ATF3. Here we analyzed the function of TFII-I in TF-1 cells during erythroid differentiation and in response to cellular stress, including unfolded protein response, hypoxia, and oxidative stress. Ablation of TFII-I leads to mild changes in the cell cycle and proliferation of TF-1 cells. Importantly, TFII-I deficiency increased the expression of the adult β-globin gene with a concomitant reduction in the expression of the fetal γ-globin genes during erythropoietin-mediated erythroid differentiation of TF-1 cells. Furthermore, TFII-I regulates genes involved in stress response, including CHOP, Elongin A, ATF3, ATF4, and Grp78, and participates in the apoptotic response to stressors. In summary, the data provide further support for the role of TFII-I in stress response and the regulation of globin genes.