title: Lymphoid to myeloid cell trans-differentiation is determined by C/EBPβ structure and post-translational modifications.
abstract: The transcription factor C/EBPβ controls differentiation, proliferation, and functionality of many cell types, including innate immune cells. A detailed molecular understanding of how C/EBPβ directs alternative cell fates remains largely elusive. A multitude of signal-dependent post-translational modifications (PTMs) differentially affect the protean C/EBPβ functions. In this study we apply an assay that converts primary mouse B lymphoid progenitors into myeloid cells in order to answer the question how C/EBPβ regulates (trans-) differentiation and determines myeloid cell fate. We found that structural alterations and various C/EBPβ PTMs determine the outcome of trans-differentiation of lymphoid into myeloid cells, including different types of monocytes/macrophages, dendritic cells, and granulocytes. The ability of C/EBPβ to recruit chromatin remodeling complexes is required for the granulocytic trans-differentiation outcome. These novel findings reveal that PTMs and structural plasticity of C/EBPβ are adaptable modular properties that integrate and rewire epigenetic functions to direct differentiation to diverse innate immune system cells, which are crucial for the organism survival.
authors.affiliation: Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Bilyana
authors.initials: B
authors.lastname: Stoilova
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kowenz-Leutz
authors.forename: Marina
authors.initials: M
authors.lastname: Scheller
authors.forename: Achim
authors.initials: A
authors.lastname: Leutz
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D007113:Immunity, Innate; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D015533:Transcriptional Activation; D059467:Transcriptome
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C545013:Cebpb protein, mouse