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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2017 (publ. 2016, arch)     Display Documents



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ID: 732165.0, MPI für molekulare Biomedizin / Jahrbuch 2017 (publ. 2016, arch)
Gadd45a is a heterochromatin relaxer that enhances iPS cell generation
Authors:Chen, K.; Long, Q.; Wang, T.; Zhao, D.; Zhou, Y.; Qi, J.; Wu, Y.; Li, S.; Chen, C.; Zeng, X.; Yang, J.; Zhou, Z.; Qin, W.; Liu, X.; Li, Y.; Li, Y.; Huang, X.; Qin, D.; Chen, J.; Pan, G.; Scholer, H. R.; Xu, G.; Liu, X.; Pei, D.
Date of Publication (YYYY-MM-DD):2016-11
Title of Journal:EMBO Rep
Volume:17
Issue / Number:11
Start Page:1641
End Page:1656
Review Status:Internal review
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Frap; Gadd45a; chromatin relaxer; heterochromatin relaxation; reprogramming
External Publication Status:published
Document Type:Article
Communicated by:Jeanine Müller-Keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Department for Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Munster, Germany. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. 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 liu_xingguo@gibh.ac.cn pei_duanqing@gibh.ac.cn.
Identifiers:ISSN:1469-3178 (Electronic) 1469-221X (Linking) %R 10.1... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/27702986 [ID No:2]
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