Department of Molecular and Cellular Biology, College of Biological Sciences
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.
- 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.
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
- Integrative Genetics and Genomics
Specialties / Focus
- Chromosome Biology
- Chromosome Dynamics and Nuclear Function
- Computational Biology
- DNA Repair
- Gene Regulation
- Genomics, Proteomics and Metabolomics
- Human Genetics and Genomics
- Integrated Genetics and Genomics
- Molecular Genetics
- MCB 162 Human Genetics, Fall
- MCB 214 Molecular Biology, Spring
- GGG 205 Lab Rotation, Fall-Winter
- Chedin Lab - 329 Briggs Hall http://www.mcb.ucdavis.edu/faculty-labs/chedin/
- Lionel Sanz and Shaheen Mohammad: Staff Scientists / Stella Hartono: Postdoctoral Researcher / John Smolka, Maika Malig, Robert Stolz and Daisy Castillo-Guzman: graduate students / Undergraduate researchers: Catherine Nugent, Miriam Rivkin, Rachel Larson.
Honors and Awards
- Basil O'Connor Starter Research Scholar Award - March of dimes foundation - 2005-2007
- CONquer CancER Now Award - Concern Foundation - 2006-2008
- Hartwell Foundation Investigator - 2012-2015
- DNA Methylation Society
- American Society of Human Genetics
- 1991 MS DNA repair and recombination University of Paris - France
- 1995 PhD DNA recombination in Bacteria University of Paris - France
Stolz R, Sulthana S, Hartono SR, Malig M, Benham CJ, Chedin F. Interplay between DNA sequence and negative superhelicity drives R-loop structures. Proceedings of the National Academy of Sciences USA. 2019; 116(13):6260-6269
Manzo SG, Hartono SR, Sanz LA, Marinello J, De Biasi S, Cossarizza A, Capranico G, Chedin F. DNA Topoisomerase I differentially modulates R-loops across the human genome. Genome Biology. 2018 Jul 30;19(1):100. doi: 10.1186/s13059-018-1478-1.
Hartono SR, Malapert A, Legros P, Bernard P, Chédin F, Vanoosthuyse V. The Affinity of the S9.6 Antibody for Double-Stranded RNAs Impacts the Accurate Mapping of R-Loops in Fission Yeast. Journal of Molecular Biology. 2018 Feb 2;430(3):272-284
Chédin F. Nascent Connections: R-Loops and Chromatin Patterning. Trends in Genetics. 2016 Dec;32(12):828-838
Sanz LA, Hartono SR, Lim YW, Steyaert S, Rajpurkar A, Ginno PA, Xu X, & Chédin* F. Prevalent, Dynamic, and Conserved R-Loop Structures Associate with Specific Epigenomic Signatures in Mammals. Molecular Cell. 2016 Jul 7;63(1):167-78
Hartono SR, Korf IF, & Chédin* F (2015) GC skew is a conserved property of unmethylated CpG island promoters across vertebrates. Nucleic Acids Research. 43(20):9729-9741.
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.
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
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.