TFII-I/Gtf2i and Erythro-Megakaryopoiesis

Abstract

TFII-I is a ubiquitously expressed transcription factor that positively or negatively regulates gene expression. TFII-I has been implicated in neuronal and immunologic diseases as well as in thymic epithelial cancer. Williams-Beuren Syndrome (WBS) is caused by a large hemizygous deletion on chromosome 7q11.23 which encompasses 26-28 genes, including GTF2I, the human gene encoding TFII-I. A subset of WBS patients has recently been shown to present with macrocytosis, a mild anemia characterized by enlarged erythrocytes. We conditionally deleted the TFII-I/Gtf2i gene in adult mice by tamoxifen induced Cre-recombination. Bone marrow cells revealed defects in erythro-megakaryopoiesis and an increase in expression of the adult β-globin gene. The data show that TFII-I acts as a repressor of β-globin gene transcription and that it is implicated in the differentiation of erythro-megakaryocytic cells.

The impact of HTR1A and HTR1B methylation combined with stress/genotype on early antidepressant efficacy

“…TFII-I as a ubiquitously expressed transcription factor can regulate gene expression negatively. 63 In addition, research has shown that the high methylation of recognition gene can affect transcription factor TFII-I binding to the region. 64 Thus, we can speculate that in patients with HTR1B rs6298 allele AA/AG and high HTR1B-3-61, expression of HTR1B receptors is higher, making early antidepressant treatment more effective.…”

Nucleoporin Nup358 drives the differentiation of myeloid-biased multipotent progenitors by modulating HDAC3 nuclear translocation

“…5A). Known regulators of hematopoiesis, including Salmonella pathogenicity island 1 (SPI1/PU.1), a key player of myeloid and lymphoid development (31)(32)(33)(34)(35); general transcription factor IIi (GTF2I), recently identified to have a function in erythro/ megakaryopoiesis (36); and the histone deacetylase 3 (HDAC3), which has been shown to regulate the activity of MPPs (37), were also altered in Nup358 −/− MPP2 clusters. Considering that these factors shuttle between the nucleus and the cytoplasm and Nup358 main function in regulating the nuclear import of specific proteins (38), we investigated whether Nup358 ablation affected their nuclear translocation.…”