Affiliation:
1. Laboratory of Molecular Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan
Abstract
Abstract
Neurons, astrocytes, and oligodendrocytes—the three major cell types that comprise the central nervous system—are generated from common multipotent neural precursor cells (NPCs). Members of the interleukin-6 family of cytokines, including leukemia inhibitory factor (LIF), induce astrocyte differentiation of NPCs by activating the transcription factor signal transducer and activator of transcription 3 (STAT3). We show here that retinoic acid (RA) facilitates LIF-induced astrocyte differentiation of NPCs. RA and LIF synergistically activate the promoter of gfap, which encodes the astrocytic marker glial fibrillary acidic protein, and a putative RA response element in the promoter was found to be critical for this activation. Histone H3 acetylation around the STAT-binding site in the gfap promoter was increased in NPCs treated with RA, allowing STAT3 to gain access to the promoter more efficiently. These results suggest that RA acts in concert with LIF to induce astrocyte differentiation of NPCs through an epigenetic mechanism that involves cross-talk between distinct signaling pathways.
Disclosure of potential conflicts of interest is found at the end of this article.
Funder
Brain Science Foundation, a Grant-in-Aid for Young Scientists, a Grant-in-Aid for Scientific Research on Priority Areas–Molecular Brain Science
Nara Institute of Science and Technology (NAIST) Global Center of Excellence (COE) Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan
Publisher
Oxford University Press (OUP)
Subject
Cell Biology,Developmental Biology,Molecular Medicine
Cited by
92 articles.
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