Offices and Labs
|1995||PhD||DNA recombination in Bacteria||University of Paris - France|
|1991||MS||DNA repair and recombination||University of Paris - France|
R-loop biology in mammals
I am focused on understanding the formation, function, and resolution of R-loop structures, a class of non-B DNA structures formed upon the annealing of an RNA strand to one strand of the DNA duplex. Genome-wide mapping data from my laboratory established that R-loop structures are the most abundant non-B DNA structures in mammalian genomes and suggests that they represent a novel type of cis-acting DNA element. Our main research themes are:
- Developing and improving genomics technologies to map R-loop formation.
- Analyzing the relationship between R-loop structures and chromatin states, including histone modifications and DNA methylation.
- Understanding the mechanisms by which R-loops are formed, sensed, and dynamically resolved.
- Elucidating how dysfunctions in R-loop metabolism is linked to human diseases, in particular neurodevelopmental and neurodegenerative disorders.
To address these topics, my group makes use of innovative (epi)genomics tools, mammalian cell culture assays, biochemical assays, proteomic methods, and computational approaches.
Department and Center Affiliations
CBS Grad Group Affiliations
Specialties / Focus
- Chromosome Biology
- Human Genetics and Genomics
- Computational Biology
- Integrated Genetics and Genomics
- Molecular Genetics
- Chromosome Dynamics and Nuclear Function
- DNA Repair
- Gene Regulation
- Genomics, Proteomics and Metabolomics
Lionel Sanz: Postdoctoral researcher / Stella Hartono, and John Smolka: graduate students / Staff Research Associate: Xiaoqin Xu / Undergraduate researchers: Kimmey Berg, Abby Lepinsky, Jenna Giafaglione, Tom Schwarz
Lim Y.W., Sanz L., Xu X., Hartono S.R., and Chédin F. (2015). DNA hypomethylation and RNA:DNA hybrid accumulation in Aicardi-Goutières syndrome. eLife. In press
Yang Y.Z., McBride K., Hensley K., Yue L., Chédin F., and Bedford M.T. (2014). Arginine methylation facilitates the recruitment of TOP3B to chromatin to prevent R-loop accumulation. Molecular Cell. 53(3):484-497.
Loomis E.W., Sanz L.A., Chédin F., and Hagerman P.J. (2014). Transcription-associated R-loop formation across the human FMR1 CGG-repeat region. PLoS Genetics. 10(4):e1004294
Powell W. T., Coulson R., Crary F. K., Wong S., Gonzales M. L., Adams S., Yasui D.H., Chédin F., and LaSalle J. M. (2013). Topotecan stabilizes R-loops to inhibit transcription in the Prader-Willi/Angelman imprinted locus. Proceedings of the National Academy of Sciences USA; 110(34):13938-13943
Ginno P. A., Lim Y.W., Lott P., Korf I., and Chédin* F. (2013). GC skew at the 5’ and 3’ Ends of Human Genes Links R-loop Formation to Epigenetic Regulation and Transcription Termination. (2013). Genome Research. 23(10):1590-1600
Gordon C.A., Hartono S.R., and Chédin* F. (2013) Inactive DNMT3B splice variants modulate de novo DNA methylation. PLoS One 2013 Jul 19;8(7):e69486.
Ginno P. A., Lott P., Christensen H. C., Korf I., and Chédin* F. (2012) R-loop formation is a distinctive characteristic of unmethylated human CpG islands. Molecular Cell, 45(6):814-825.