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- The transcription factor PITX1 drives astrocyte differentiation by regulating the SOX9 gene
- Jeong Su Byun; Mihee Oh; Seonha Lee; Jung-Eun Gil; Yeajin Mo; Bonsu Ku; Won Kon Kim; Kyoung-Jin Oh; Eun-Woo Lee; Kwang-Hee Bae; Sang Chul Lee; Baek Soo Han
- Bibliographic Citation
- Journal of Biological Chemistry, vol. 295, no. 39, pp. 13677-13690
- Publication Year
- Astrocytes perform multiple essential functions in the developing and mature brain, including regulation of synapse formation, control of neurotransmitter release and uptake, and maintenance of extracellular ion balance. As a result, astrocytes have been implicated in the progression of neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. Despite these critical functions, the study of human astrocytes can be difficult because standard differentiation protocols are time-consuming and technically challenging, but a differentiation protocol recently developed in our laboratory enables the efficient derivation of astrocytes from human embryonic stem cells. We used this protocol along with microarrays, luciferase assays, electrophoretic mobility shift assays, and ChIP assays to explore the genes involved in astrocyte differentiation. We demonstrate that paired-like homeodomain transcription factor 1 (PITX1) is critical for astrocyte differentiation. PITX1 overexpression induced early differentiation of astrocytes, and its knockdown blocked astrocyte differentiation. PITX1 overexpression also increased and PITX1 knockdown decreased expression of sex-determining region Y box 9 (SOX9), known initiator of gliogenesis, during early astrocyte differentiation. Moreover, we determined that PITX1 activates the SOX9 promoter through a unique binding motif. Taken together, these findings indicate that PITX1 drives astrocyte differentiation by sustaining activation of the SOX9 promoter.
- Amer Soc Biochemistry Molecular Biology Inc
- Appears in Collections:
- Division of Research on National Challenges > Biodefense Research Center > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
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