Fei Li

Associate Professor of Biology

Education

Ph.D., The University of Texas at Austin

M.S., University of Louisiana at Monroe

B.S. Sichuan University, China

Areas of Research/Interest

epigenetics, epigenomics, chromatin

Research

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.

Job Opportunities

Post-doctoral and research assistant positions are available in Dr. Li’s laboratory.

Selected Works

Qianhua Dong, Fei Li. Cell cycle control of kinetochore assembly. Nucleus 2022 Dec;13(1):208-220. doi: 10.1080/19491034.2022.2115246.

Hyoju Ban, Wenqi Sun, Yong Chen, Fei Li. Phase separation of Dri1 contributes to heterochromatin formation in Schizosaccharomyces pombe. MicroPubl Biol. 2022 Apr 19;2022:10.17912/micropub.biology.000559. doi: 10.17912/micropub.biology.000559.

Li Qin, Ling-hui Tang, Jia-shu Xu, Xian-hui Zhang, Yun Zhu, Chun-rui Zhang, Mei-hua Wang, Xue-lei Liu, Fei Li, Fei Sun, Min Su, Yujia Zhai, Yu-hang Chen. Cryo-EM structure and electrophysiological characterization of ALMT from Glycine max reveal a previously uncharacterized class of anion channels. Science Advances 2022 Mar 4;8(9):eabm3238. doi: 10.1126/sciadv.abm3238. 

Qianhua Dong, Jinpu Yang, Jinxin Gao, Fei Li. Recent insights into mechanisms preventing ectopic centromere formation. Open Biology 2021 Sep;11(9):210189. doi: 10.1098/rsob.210189.

Qianhua Dong, Xue-lei Liu, Xiao-hui Wang, Yu Zhao, Yu-hang Chen, Fei Li. Ccp1-Ndc80 switch at the N-terminus ofCENP-T regulates kinetochore assembly. Proc Natl Acad Sci U S A. 2021 Nov 30;118(48):e2104459118. doi: 10.1073/pnas.2104459118.

Hyoju Ban, Wenqi Sun, Yu-Hang Chen, Yong Chen, Fei Li. Dri1 mediates heterochromatin assembly via RNAi and histone deacetylation (https://pubmed.ncbi.nlm.nih.gov/33693625/). Genetics 2021; 218(1):iyab032. doi: 10.1093/genetics/iyab032

Ya-nan Deng, Hamdy Kashtoh, Quan Wang, Guang-xiao Zhen, Qi-yu Li, Ling-hui Tang, Hai-long Gao, Chun-rui Zhang, Li Qin, Min Su, Fei Li, Xia-he Huang, Ying-chun Wang, Qi Xie, Oliver B. Clarke, Wayne A. Hendrickson, and Yu-hang Chen. Structure and activity of SLAC1 channels for stomatal signaling in leaves (https://pubmed.ncbi.nlm.nih.gov/33926963/). Proc Natl Acad Sci U S A. 2021;118(18):e2015151118. doi: 10.1073/pnas.2015151118.

Martina Weigt, Qingsong Gao, Hyoju Ban, Haijin He, Guido Mastrobuoni, Stefan Kempa, Wei Chen, Fei Li. Rbm10 facilitates heterochromatin assembly via the Clr6 HDAC complex (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816512/). Epigenetics & Chromatin 2021;14 (1), 1-13. doi: 10.1186/s13072-021-00382-y.

Xiaohui Wang, Min Su, Feng Gao, Wenjun Xie, Yang Zeng, Delin Li, Xuelei Liu, Hong Zhao, Li Qin, Fei Li, Qun Liu, Oliver B Clarke, Sin Man Lam, Guanghou Shui, Wayne A Hendrickson, Yu-hang Chen. Structural basis for activity of TRIC counter-ion channels in calcium release. Proc Natl Acad Sci U S A. 2019; PMID: 30770441

David Aristizabal-Corrales, Jinpu Yang and Fei Li. (Highlighted in Genetics). Cell Cycle-Regulated Transcription of CENP-A by the MBF Complex Ensures Optimal Level of CENP-A for Centromere Formation. Genetics 2019; PMID: 30635289  

Jinpu Yang, Siyu Sun, Shu Zhang, Marlyn Gonzalez, Qianhua Dong, Zhongxuan Chi, Yu-hang Chen, Fei Li. Heterochromatin and RNAi regulate centromeres by protecting CENP-A from ubiquitin-mediated degradation. PLoS Genetics 2018; 14(8):e1007572. doi: 10.1371/journal.pgen.1007572. eCollection 2018 Aug.

Wang Li, Heyong Wang, Yan Yang, Tian Zhao, Zhixiong Zhang, Ye Tian, Zhaomie Shi, Xiaojun Peng, Fei Li, Yonghong Feng, Lei Zhang, Gening Jiang, Fan Zhang. Integrative Analysis of Proteome and Ubiquitylome Reveals Unique Features of Lysosomal and Endocytic Pathways in Gefitinib Resistant Non‐Small Cell Lung Cancer Cells. Proteomics 2018; 18(15):e1700388. doi: 10.1002/pmic.201700388.

Jinpu Yang, Fei Li. In Situ Chromatin-Binding Assay Using Epifluorescent Microscopy in S. pombe. Methods Mol Biol. 2018; 1721:155-165. doi: 10.1007/978-1-4939-7546-4_14.

Qianhua Dong, Fei Li. Antibody Pull-Down Experiments in Fission Yeast. Methods Mol Biol. 2018;1721:117-123. doi: 10.1007/978-1-4939-7546-4_11.

Haijin He, Yang Li, Qianhua Dong, An-Yun Chang, Feng Gao, Zhongxuan Chi, Min Su, Faben Zhang, Hyoju Ban, Rob Martienssen, Yu-hang Chen*, and Fei Li*. Coordinated regulation of heterochromatin inheritance by Dpb3–Dpb4 complex. Proc Natl Acad Sci U S A. 2017; 114 (47) 12524-12529

Qianhua Dong, Feng-xiang Yin, Feng Gao, Yuan Shen, Yang Li, Haijin He, Marlyn Gonzalez, Jinpu Yang, Shu Zhang, Min Su, Yu-hang Chen*, Fei Li*. Ccp1 homodimer mediates chromatin integrity by antagonizing CENP-A loading. Molecular Cell 2016; 64(1):79-91.

Jinpu Yang, and Fei Li. Are all repeats created equal? Understanding DNA repeats at an individual level. Current Genetics 2016, DOI: 10.1007/s00294-016-0619-x. Epub June 03.

Lingzhi Kong, Peng Zhang, Wang Li, Yan Yang, Ye Tian, Xujun Wang, Sujun Chen, Yuxin Yang, Tianhao Huang, Tian Zhao, Liang Tang, Bo Su, Fei Li, X. Shirley Liu, and Fan Zhang. KDM1A promotes tumor cell invasion by silencing TIMP3 in non-small cell lung cancer cells. Oncotarget 2016 Apr 2. doi: 10.18632/oncotarget.8563.

Haijin He, Shu Zhang, Danni Wang, Andreas Hochwagen and Fei Li. Condensin promotes position effects within tandem DNA repeats via the RITS complex. Cell Reports 2016; DOI: 10.1016/j.celrep.2016.01.006. Epub Jan 28.

Marlyn Gonzalez, Haijin He, Qianhua Dong, Siyu Sun, and Fei Li. Ectopic centromere nucleation by CENP-A in fission yeast. Genetics 2014;198(4):1433-46.

Haijin He, Marlyn Gonzalez, Fan Zhang, Fei Li. DNA replication components as regulators of epigenetic inheritance-lesson from fission yeast centromere. Protein Cell 2014; 5(6):411-9

Meru J. Sadhu, Qiaoning Guan, Fei Li, Jade Sales-Lee, Anthony T. Iavarone, Ming C. Hammond, W. Zacheus Cande, and Jasper Rine. Nutritional Control of Epigenetic Processes in Yeast and Human Cells. Genetics 2013; 195:831-844.

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