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ATP-Dependent Chromatin Remodeler CHD9 Controls the Proliferation of Embryonic Stem Cells in a Cell Culture Condition-Dependent Manner

Department of Stem Cell and Regenerative Biotechnology and Humanized Pig Center (SRC), Konkuk University, Seoul 05029, Korea
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Biology 2020, 9(12), 428; https://doi.org/10.3390/biology9120428
Received: 19 October 2020 / Revised: 25 November 2020 / Accepted: 26 November 2020 / Published: 27 November 2020
Chromodomain-helicase-DNA-binding protein 9 (CHD9) has been implicated in the regulation of gene expression, yet its precise role in the maintenance of mammalian embryonic stem cell (ESC) remains unclear. In the present study, we demonstrated that mouse CHD9 controls the cell cycle of ESCs in a cell culture condition-dependent manner by modulating the accessibility of transcription factors to their target genomic elements. Our study, therefore, has not only established how CHD9 finetunes chromatin structure during animal development but provided a potential target for genetic screening of aberrant development in in vitro produced embryos.
Emerging evidence suggests that chromodomain-helicase-DNA-binding (CHD) proteins are involved in stem cell maintenance and differentiation via the coordination of chromatin structure and gene expression. However, the molecular function of some CHD proteins in stem cell regulation is still poorly understood. Herein, we show that Chd9 knockdown (KD) in mouse embryonic stem cells (ESCs) cultured in normal serum media, not in 2i-leukemia inhibitory factor (LIF) media, causes rapid cell proliferation. This is caused by transcriptional regulation related to the cell cycle and the response to growth factors. Our analysis showed that, unlike the serum cultured-Chd9 KD ESCs, the 2i-LIF-cultured-Chd9 KO ESCs displayed elevated levels of critical G1 phase regulators such as p21 and p27. Consistently, the DNA binding sites of CHD9 overlap with some transcription factor DNA motifs that are associated with genes regulating the cell cycle and growth pathways. These transcription factors include the cycle gene homology region (CHR), Arid5a, and LIN54. Collectively, our results provide new insights into CHD9-mediated gene transcription for controlling the cell cycle of ESCs. View Full-Text
Keywords: CHD9; chromatin structure; ES cell; cell cycle; transcription CHD9; chromatin structure; ES cell; cell cycle; transcription
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MDPI and ACS Style

Yoo, H.; La, H.; Lee, E.J.; Choi, H.-J.; Oh, J.; Thang, N.X.; Hong, K. ATP-Dependent Chromatin Remodeler CHD9 Controls the Proliferation of Embryonic Stem Cells in a Cell Culture Condition-Dependent Manner. Biology 2020, 9, 428. https://doi.org/10.3390/biology9120428

AMA Style

Yoo H, La H, Lee EJ, Choi H-J, Oh J, Thang NX, Hong K. ATP-Dependent Chromatin Remodeler CHD9 Controls the Proliferation of Embryonic Stem Cells in a Cell Culture Condition-Dependent Manner. Biology. 2020; 9(12):428. https://doi.org/10.3390/biology9120428

Chicago/Turabian Style

Yoo, Hyunjin, Hyeonwoo La, Eun Joo Lee, Hee-Jin Choi, Jeongheon Oh, Nguyen Xuan Thang, and Kwonho Hong. 2020. "ATP-Dependent Chromatin Remodeler CHD9 Controls the Proliferation of Embryonic Stem Cells in a Cell Culture Condition-Dependent Manner" Biology 9, no. 12: 428. https://doi.org/10.3390/biology9120428

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