| First Author | Bayer M | Year | 2022 |
| Journal | Genes Dev | Volume | 36 |
| Issue | 15-16 | Pages | 901-915 |
| PubMed ID | 36167471 | Mgi Jnum | J:332143 |
| Mgi Id | MGI:7408617 | Doi | 10.1101/gad.349696.122 |
| Citation | Bayer M, et al. (2022) Tnpo3 enables EBF1 function in conditions of antagonistic Notch signaling. Genes Dev 36(15-16):901-915 |
| abstractText | Transcription factor EBF1 (early B cell factor 1) acts as a key regulator of B cell specification. The transcriptional network in which EBF1 operates has been extensively studied; however, the regulation of EBF1 function remains poorly defined. By mass spectrometric analysis of proteins associated with endogenous EBF1 in pro-B cells, we identified the nuclear import receptor Transportin-3 (Tnpo3) and found that it interacts with the immunoglobulin-like fold domain of EBF1. We delineated glutamic acid 271 of EBF1 as a critical residue for the association with Tnpo3. EBF1(E271A) showed normal nuclear localization; however, it had an impaired B cell programming ability in conditions of Notch signaling, as determined by retroviral transduction of Ebf1 (-/-) progenitors. By RNA-seq analysis of EBF1(E271A)-expressing progenitors, we found an up-regulation of T lineage determinants and down-regulation of early B genes, although similar chromatin binding of EBF1(E271A) and EBF1(wt) was detected in pro-B cells expressing activated Notch1. B lineage-specific inactivation of Tnpo3 in mice resulted in a block of early B cell differentiation, accompanied by a down-regulation of B lineage genes and up-regulation of T and NK lineage genes. Taken together, our observations suggest that Tnpo3 ensures B cell programming by EBF1 in nonpermissive conditions. |
