[논문]The transcription factor PITX1 drives astrocyte differentiation by regulating the SOX9 gene

Byun, Jeong Su; Oh, Mihee; Lee, Seonha; Gil, Jung-Eun; Mo, Yeajin; Ku, Bonsu; Kim, Won-Kon; Oh, Kyoung-Jin; Lee, Eun-Woo; Bae, Kwang-Hee; Lee, Sang Chul; Han, Baek-Soo

doi:10.1074/jbc.RA120.013352

[해외논문] The transcription factor PITX1 drives astrocyte differentiation by regulating the SOX9 gene 원문보기

The Journal of biological chemistry, v.295 no.39, 2020년, pp.13677 - 13690

Byun, Jeong Su (Biodefence Research Center, Korea Research Institute of Bioscience and Biotechnology, Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea) , Oh, Mihee (Biodefence Research Center, Korea Research Institute of Bioscience and Biotechnology, Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea) , Lee, Seonha (Biodefence Research Center, Korea Research Institute of Bioscience and Biotechnology, Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea) , Gil, Jung-Eun (Biodefence Research Center, Korea Research Institute of Bioscience and Biotechnology, Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea) , Mo, Yeajin (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea) , Ku, Bonsu (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea) , Kim, Won-Kon (Department of Functional Genomics, University of Science and Technology of Korea, Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea) , Oh, Kyoung-Jin (Departmen) , Lee, Eun-Woo , Bae, Kwang-Hee , Lee, Sang Chul , Han, Baek-Soo

Abstract ▼ AI-Helper

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.

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