Gadd45a is a heterochromatin relaxer that enhances iPS cell generation |
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| Authors: | Tao Wang Danyun Zhao Yanshuang Zhou Juntao Qi Yi Wu Shengbiao Li Chunlan Chen Xiaoming Zeng Jianguo Yang Zisong Zhou Weiwen Qin Xiyin Liu Yuxing Li Yingying Li Xiaofen Huang Dajiang Qin Jiekai Chen Guangjin Pan Hans R Schöler Guoliang Xu Xingguo Liu Duanqing Pei |
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| Institution: | 1. Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China;2. Department for Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany;3. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China |
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| Abstract: | Reprogramming of somatic cells to induced pluripotent stem cells rewrites the code of cell fate at the chromatin level. Yet, little is known about this process physically. Here, we describe a fluorescence recovery after photobleaching method to assess the dynamics of heterochromatin/euchromatin and show significant heterochromatin loosening at the initial stage of reprogramming. We identify growth arrest and DNA damage‐inducible protein a (Gadd45a) as a chromatin relaxer in mouse embryonic fibroblasts, which also enhances somatic cell reprogramming efficiency. We show that residue glycine 39 (G39) in Gadd45a is essential for interacting with core histones, opening chromatin and enhancing reprogramming. We further demonstrate that Gadd45a destabilizes histone–DNA interactions and facilitates the binding of Yamanaka factors to their targets for activation. Our study provides a method to screen factors that impact on chromatin structure in live cells, and identifies Gadd45a as a chromatin relaxer. |
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| Keywords: | chromatin relaxer
FRAP
Gadd45a heterochromatin relaxation reprogramming |
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