Tnpo3 enables EBF1 function in conditions of antagonistic Notch signaling

Bayer, Marc; Boller, Sören; Ramamoothy, Senthilkumar; Zolotarev, Nikolay; Cauchy, Pierre; Iwanami, Norimasa; Mittler, Gerhard; Boehm, Thomas; Grosschedl, Rudolf

doi:10.1101/gad.349696.122

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Tnpo3 enables EBF1 function in conditions of antagonistic Notch signaling

MPS-Authors

Bayer, Marc
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Boller, Sören
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Ramamoothy, Senthilkumar
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Zolotarev, Nikolay
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Cauchy, Pierre
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Iwanami, Norimasa
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191219

Mittler, Gerhard
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons190993

Boehm, Thomas
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191076

Grosschedl, Rudolf
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource

http://genesdev.cshlp.org/content/36/15-16/901
(Publisher version)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Bayer, M., Boller, S., Ramamoothy, S., Zolotarev, N., Cauchy, P., Iwanami, N., et al. (2022). Tnpo3 enables EBF1 function in conditions of antagonistic Notch signaling. Genes and Development, 36, 901-915. doi:10.1101/gad.349696.122.

Cite as: https://hdl.handle.net/21.11116/0000-000B-C1EF-E

Abstract

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.