Assistant Professor of Biology
Ph.D., The University of Texas at Austin; M.S., University of Louisiana at Monroe; B.S. Sichuan University, China.
|New York University|
|Department of Biology|
|1009 Silver Center|
|100 Washington Square East|
|New York, NY 10003-6688|
Areas of Research/Interest:
epigenetics, epigenomics, chromatin
Epigenetics is the study of heritable changes in phenotype that occur without changes in DNA sequence. Epigenetic mechanisms are essential for many cellular processes, such as gene-expression regulation, genome organization and cell-fate determination. Defects in epigenetic regulation have been implicated in a variety of diseases, including cancer. The aim of our research is to understand the fundamental principles of epigenetic regulation. Toward this goal, we have chosen to study the fission yeast (Schizosaccharomyces pombe), a model eukaryotic organism well suited to a combination of powerful experimental approaches, including genetics, cell biology, biochemistry and genomics. Importantly, fission yeast contains many conserved epigenetic components, and has thus emerged as a premier model for epigenetic study.
Epigenetic Regulation of Heterochromatin
In eukaryotes, DNA is packaged together with histone proteins into an ordered, highly complex chromatin structure. Chromatin exists in two forms: euchromatin and heterochromatin. Euchromatin is typically transcriptionally active and loosely packaged, whereas heterochromatin is gene-poor and appears highly compact throughout the cell cycle. Heterochromatin is a classic example of epigenetic phenomena and plays an important role in gene regulation, chromosome segregation and genome stability. Taking advantage of powerful genetic and biochemical approaches available in fission yeast, we have identified multiple key heterochromatin factors. We aim to understand the epigenetic mechanisms that regulate establishment and maintenance of heterochromatin.
Epigenetic Regulation of Centromeres
Centromeres are specific chromosomal loci where the kinetochore, a multiprotein complex, is assembled. Kinetochores mediate attachment of spindle microtubules to centromeres, ensuring proper segregation of chromosomes during mitosis and meiosis. A fundamental question in biology is how centromere identity is defined and maintained through generations. In most eukaryotes, centromere assembly and propagation are regulated by epigenetic mechanisms. Centromere Protein-A (CENP-A), a centromere-specific histone 3 variant, represents the most likely candidate for the epigenetic mark that specifies centromere identity. CENP-A provides a structural and functional foundation for the assembly of kinetochores. Defects in the regulation of CENP-A are catastrophic for cells and result in chromosome mis-segregation and aneuploidy, or an abnormal number of chromosomes, the hallmark of human cancers. We are currently using biochemical, genetic, cytological and genomic approaches to dissect the gene regulatory network mediating the faithful inheritance of centromeres.
Post-doctoral and research assistant positions are available in Dr. Li’s laboratory.
Pew Scholar in the Biomedical Sciences, 2013; Memorial Research Scholarship, University of Texas at Austin, 2002
Marlyn Gonzalez, Haijin He, Siyu Sun, Chen Li, and Fei Li*. Cell cycle-dependent deposition of CENP-A requires the Dos1/2- Cdc20 Complex. Proc Natl Acad Sci U S A. 2013 110(2):606-11
Marlyn Gonzalez, and Fei Li*. DNA replication, RNAi and epigenetic inheritance. Epigenetics 2012; 7(1):14-19
Mikel Zaratiegui, Stephane Castel, Danielle V. Irvine, Anna Kloc, Jie Ren, Fei Li, Elisa de Castro, Laura Marín, An-Yun Chang, Derek Goto, W. Zacheus Cande, Francisco Antequera, Benoit Arcangioli, and Rob Martienssen. RNAi promotes heterochromatic silencing through replication-coupled release of RNA pol II. Nature 2011; 479(7371):135-8
Fei Li*, Rob Martienssen, and Zacheus Cande. Coordination of DNA Replication, Histone modification and siRNA Production by the Rik1/Dos2 Complex. Nature 2011; 475(7355):244-8
Fei Li*, Maite Huarte, Mikel Zaratiegui, Matthew W. Vaughn, Yang Shi, Rob Martienssen, and W. Zacheus Cande*. Lid2 is required for coordinating H3K4 and H3K9 methylation of heterochromatin and euchromatin. Cell 2008; 135: 272-83
Ian J. MacRae, Fei Li, Kaihong Zhou, W. Zacheus Cande, and Jennifer A. Doudna. Structure of Dicer and mechanistic implications for RNAi. Cold Spring Harb Symp Quant Biol. 2006; 71:73-80
Ian J. MacRae, Kaihong Zhou, Fei Li, Adrian Repic, Angela N. Brooks, W. Zacheus Cande, Paul Adams, and Jennifer Doudna. Structural basis for double-stranded RNA processing by Dicer. Science 2006; 311 (5758): 195- 8
Fei Li, Derek B. Goto, Mikel Zaratiegui, Xie Tang, Rob Martienssen, and W. Zacheus Cande. Two novel proteins, Dos1 and Dos2, interact with Rik1 to regulate heterochromatic RNA Interference and histone modification. Curr Biol. 2005; 15(16):1448-57
Satoru Uzawa, Fei Li, Ye Jin, Kent McDonald, Michael Braunfield, David Agard, and W. Zacheus Cande. Spindle pole body duplication in fission yeast occurs at the G1/S Boundary but maturation is blocked until exit from S by an event downstream of Cdc10. Mol Biol Cell. 2004; 15(12):5219-30
Fei Li, Stephen P. Holloway, Jaesung Lee, and David L. Herrin. Nuclear genes that promote splicing of group I introns in the chloroplast 23S rRNA and psbA genes in Chlamydomonas reinhardtii. Plant J. 2002; 32(4):467-80
Fei Li and David L. Herrin. FUGOID: functional genomics of organellar introns database. Nucleic Acids Res. 2002; 30(1):385-6
* corresponding author