Lymphoid to myeloid cell trans-differentiation is determined by C/EBP? structure and post-translational modifications.

ABSTRACT: The transcription factor C/EBP? controls differentiation, proliferation, and functionality of many cell types, including innate immune cells. A detailed molecular understanding of how C/EBP? directs alternative cell fates remains largely elusive. A multitude of signal-dependent post-translational modifications (PTMs) differentially affect the protean C/EBP? 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/EBP? regulates (trans-) differentiation and determines myeloid cell fate. We found that structural alterations and various C/EBP? 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/EBP? to recruit chromatin remodeling complexes is required for the granulocytic trans-differentiation outcome. These novel findings reveal that PTMs and structural plasticity of C/EBP? 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.

SUBMITTER: Stoilova B 

PROVIDER: S-EPMC3674013 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature