Regularly spaced tyrosines in EBF1 mediate BRG1 recruitment and formation of nuclear subdiffractive clusters.

Autor: Zolotarev N; Laboratory of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg 79108, Germany.; Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg 79108, Germany., Wang Y; Laboratory of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg 79108, Germany., Du M; Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg 79108, Germany., Bayer M; Laboratory of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg 79108, Germany., Grosschedl A; Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg 79108, Germany., Cisse I; Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg 79108, Germany., Grosschedl R; Laboratory of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg 79108, Germany; grosschedl@ie-freiburg.mpg.de.
Jazyk: angličtina
Zdroj: Genes & development [Genes Dev] 2024 Feb 13; Vol. 38 (1-2), pp. 4-10. Date of Electronic Publication: 2024 Feb 13.
DOI: 10.1101/gad.350828.123
Abstrakt: B lineage priming by pioneer transcription factor EBF1 requires the function of an intrinsically disordered region (IDR). Here, we examine the role of regularly spaced tyrosines in the IDR as potential determinants of IDR function and activity of EBF1. We found that four Y > A mutations in EBF1 reduced the formation of condensates in vitro and subdiffractive clusters in vivo. Notably, Y > A mutant EBF1 was inefficient in promoting B cell differentiation and showed impaired chromatin binding, recruitment of BRG1, and activation of specific target genes. Thus, regularly spaced tyrosines in the IDR contribute to the biophysical and functional properties of EBF1.
(© 2024 Zolotarev et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze: MEDLINE