Journal article
Visualization of aging-associated chromatin alterations with an engineered TALE system
Cell research, Vol.27(4), pp.483-504
04/2017
DOI: 10.1038/cr.2017.18
PMCID: PMC5385610
PMID: 28139645
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
.
Details
- Title: Subtitle
- Visualization of aging-associated chromatin alterations with an engineered TALE system
- Creators
- Ruotong Ren - , Beijing 100101Liping Deng - , Beijing 100101Yanhong Xue - , Beijing 100101Keiichiro Suzuki - , 10010 North Torrey Pines Road, La Jolla, CA 92037Weiqi Zhang - , Beijing 100101Jun Wu - , 10010 North Torrey Pines Road, La Jolla, CA 92037Liang Sun - , Beijing 100730Xiaojun Gong - , Beijing 100038Huiqin Luan - , Beijing 100101Fan Yang - , Guangzhou, Guangdong 510632Zhenyu Ju - , Hangzhou, Zhejiang 311121Xiaoqing Ren - , Beijing 100101Si Wang - , Beijing 100101Hong Tang - , Beijing 100038Lingling Geng - , Beijing 100101Weizhou Zhang - , Iowa City, IA 52242Jian Li - , Beijing 100730Jie Qiao - , Beijing 100191Tao Xu - University of Chinese Academy of SciencesJing Qu - , Beijing 100049Yang Yu - Peking University Third HospitalGuang-Hui Liu - , Beijing 100101
- Resource Type
- Journal article
- Publication Details
- Cell research, Vol.27(4), pp.483-504
- DOI
- 10.1038/cr.2017.18
- PMID
- 28139645
- PMCID
- PMC5385610
- NLM abbreviation
- Cell Res
- ISSN
- 1001-0602
- eISSN
- 1748-7838
- Publisher
- Nature Publishing Group
- Alternative title
- An engineered TALE system for live imaging
- Language
- English
- Date published
- 04/2017
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984083270202771
Metrics
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