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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell+Res 2017 ; 27 (4): 483-504 Nephropedia Template TP
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Visualization of aging-associated chromatin alterations with an engineered TALE system #MMPMID28139645
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; Xu T; Qu J; Liu GH
Cell Res 2017[Apr]; 27 (4): 483-504 PMID28139645show ga
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.