Journal
G3-GENES GENOMES GENETICS
Volume 7, Issue 10, Pages 3295-3303Publisher
GENETICS SOCIETY AMERICA
DOI: 10.1534/g3.117.300141
Keywords
C. elegans; circular DNAs; eccDNA; 3D genome architecture; circulome; mucin
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Funding
- National Institutes of Health (NIH) [R01GM37706]
- Stanford Medicine Dean's Postdoctoral Fellowship
- Human Frontiers Science Program Postdoctoral Fellowship [LT000517/2011]
- NIH/National Science Foundation Joint Program in Mathematical Biology [DMS-0800929]
- Cecil and Ida Green Endowment
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Investigations aimed at defining the 3D configuration of eukaryotic chromosomes have consistently encountered an endogenous population of chromosome-derived circular genomic DNA, referred to as extrachromosomal circular DNA (eccDNA). While the production, distribution, and activities of eccDNAs remain understudied, eccDNA formation from specific regions of the linear genome has profound consequences on the regulatory and coding capabilities for these regions. Here, we define eccDNA distributions in Caenorhabditis elegans and in three human cell types, utilizing a set of DNA topology-dependent approaches for enrichment and characterization. The use of parallel biophysical, enzymatic, and informatic approaches provides a comprehensive profiling of eccDNA robust to isolation and analysis methodology. Results in human and nematode systems provide quantitative analysis of the eccDNA loci at both unique and repetitive regions. Our studies converge on and support a consistent picture, in which endogenous genomic DNA circles are present in normal physiological states, and in which the circles come from both coding and noncoding genomic regions. Prominent among the coding regions generating DNA circles are several genes known to produce a diversity of protein isoforms, with mucin proteins and titin as specific examples.
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