FUSE binding protein 1 (FUBP1) expression is upregulated by T-cell acute lymphocytic leukemia protein 1 (TAL1) and required for efficient erythroid differentiation

Abstract

During erythropoiesis, haematopoietic stem cells (HSCs) differentiate in successive steps of commitment and specification to mature erythrocytes. This differentiation process is controlled by transcription factors that establish stage- and cell type-specific gene expression. In this study, we demonstrate that FUSE binding protein 1 (FUBP1), a transcriptional regulator important for HSC self-renewal and survival, is regulated by T-cell acute lymphocytic leukaemia 1 (TAL1) in erythroid progenitor cells. TAL1 directly activates the FUBP1 promoter, leading to increased FUBP1 expression during erythroid differentiation. The binding of TAL1 to the FUBP1 promoter is highly dependent on an intact GATA sequence in a combined E-box/GATA motif. We found that FUBP1 expression is required for efficient erythropoiesis, as FUBP1-deficient progenitor cells were limited in their potential of erythroid differentiation. Thus, the finding of an interconnection between GATA1/TAL1 and FUBP1 reveals a molecular mechanism that is part of the switch from progenitor- to erythrocyte-specific gene expression. In summary, we identified a TAL1/FUBP1 transcriptional relationship, whose physiological function in haematopoiesis is connected to proper erythropoiesis.

NORAD orchestrates endometrial cancer progression by sequestering FUBP1 nuclear localization to promote cell apoptosis

“…Our study also revealed that FUBP1 was upregulated in EC, and knockdown of FUBP1 remarkably enhanced cell apoptosis. TAL1 was reported to bind to the FUBP1 promoter and activate its transcription in erythroid differentiation 36 . FUBP1 was also regulated by the PI3K/AKT/mTOR pathway and caspase protein in liver cancer 37 or targeted by miR-16 in breast and gastric cancer 38 .…”

High expression of FUSE binding protein 1 in breast cancer stimulates cell proliferation and diminishes drug sensitivity

“…The human far upstream element (FUSE) binding protein 1 (FBP1) is a multifunctional DNA-and RNA-binding protein involved in diverse cellular processes, which regulates transcription, splicing and translation (12). FBP1 promotes cell proliferation, enhances cell migration and inhibits apoptosis by modulating complex networks (13). FBP1 is overexpressed in a variety of malignant tumors, such as hepatocellular carcinoma, ovarian cancer, nasopharyngeal carcinoma and breast cancer (5,(14)(15)(16).…”

“…Therefore, FBP1 is considered a proto-oncogene. FBP1 was originally identified as a factor that binds the FUSE motif in the promoter of the oncogene c-Myc (13). Moreover, c-Myc, the deubiquitinating enzyme ubiquitin specific peptidase 29 and the cell cycle inhibitor p21, are regulated by FBP1 (17).…”

The transcription factor TAL1 and miR-17-92 create a regulatory loop in hematopoiesis

“…Erythroleukemic K562 and T-cell leukemic Jurkat cells were cultured in RPMI-1640 and HEK293T cells in DMEM medium supplemented with 10% fetal calf serum, 2 mM glutamine and 1% penicillin/streptomycin. Lentiviral particles were produced in HEK293T cells as described previously 39 . K562 and Jurkat cells were transduced with TAL1 knockdown constructs targeting the following sites: shTAL1#1 5′- ATTCTTGCTGAGCTTCTTGTC-3′; shTAL1#2 5′-TCAATTCGGA ACATAGACCA-3′.…”

“…Transfection of K562 cells, cell lysis, luciferase measurement and value normalization and analysis were performed as described previously 40 . HEK293T cells were transfected and lysed as described previously 39 . β-galactosidase activity for normalization was measured 5 min after addition of buffer (11.1 mM MgCl2, 50 mM β-Mercaptoethanol, 3.25 mM o-Nitrophenyl-β- d -galactopyranosid (ONPG), 74.4 mM sodium phosphate) at an absorption of 420 nm.…”