Visualization of aging-associated chromatin alterations with an engineered TALE system

Ruotong Ren, Liping Deng, Yanhong Xue, Keiichiro Suzuki, Weiqi Zhang, Yang Yu, Jun Wu, Liang Sun, Xiaojun Gong, Huiqin Luan, Fan Yang, Zhenyu Ju, Xiaoqing Ren, Si Wang, Hong Tang, Lingling Geng, Weizhou Zhang, Jian Li, Jie Qiao, Tao XuJing Qu, Guang Hui Liu

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Visualization of specific genomic loci in live cells is a prerequisite for the investigation of dynamic changes in chromatin architecture during diverse biological processes, such as cellular aging. However, current precision genomic imaging methods are hampered by the lack of fluorescent probes with high specificity and signal-to-noise contrast. We find that conventional transcription activator-like effectors (TALEs) tend to form protein aggregates, thereby compromising their performance in imaging applications. Through screening, we found that fusing thioredoxin with TALEs prevented aggregate formation, unlocking the full power of TALE-based genomic imaging. Using thioredoxin-fused TALEs (TTALEs), we achieved high-quality imaging at various genomic loci and observed aging-associated (epi) genomic alterations at telomeres and centromeres in human and mouse premature aging models. Importantly, we identified attrition of ribosomal DNA repeats as a molecular marker for human aging. Our study establishes a simple and robust imaging method for precisely monitoring chromatin dynamics in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)483-504
Number of pages22
JournalCell Research
Volume27
Issue number4
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Keywords

  • aging
  • centromere
  • ribosomal DNA repeat
  • telomere
  • thioredoxin-fused TALE

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Ren, R., Deng, L., Xue, Y., Suzuki, K., Zhang, W., Yu, Y., Wu, J., Sun, L., Gong, X., Luan, H., Yang, F., Ju, Z., Ren, X., Wang, S., Tang, H., Geng, L., Zhang, W., Li, J., Qiao, J., ... Liu, G. H. (2017). Visualization of aging-associated chromatin alterations with an engineered TALE system. Cell Research, 27(4), 483-504. https://doi.org/10.1038/cr.2017.18