Phase separation, Epigenetics, Chromatin, Genome organization, Single-molecule imaging
2019— Associate Professor, Department of Chemistry, University of Colorado Denver
2012—2019 Assistant Professor, Department of Chemistry, University of Colorado Denver
2005—2012 Research Associate, HHMI/UM Ann Arbor
2002—2005 Postdoctoral Fellow, Department of Chemistry, University of Cambridge UK
1999—2002 Ph.D. in Macromolecular Chemistry and Physics, Jilin University, P. R. China
1997—1999 M.S. in Organic Chemistry, Department of Chemistry, Jilin University, P. R. China
1993—1997 B.Eng. in Polymer Material Science and Engineering, Department of Chemistry, Jilin University, P. R. China
2021 Significant Papers from 100+ Years of Journal of Biological Chemistry (46 in total)
2021 “Perseverance Award” for CU Denver’s Pandemic Research and Creative Activities
2020 CU Denver Campus-wide Award in Research and Creative Activities
2020 CU Denver CLAS Excellence in Research and Creative Activities Award
2019 “The year in Journal of Biological Chemistry” for 2019
2016 CU Denver CLAS Excellence in Research and Creative Activities Award
2015 “The year in Journal of Biological Chemistry” for 2015
2015 The Paper of the Week of the Journal of Biological Chemistry
2015 University (Downtown and Anschutz) Nomination for Pew Scholars
2002 Doctoral Degree with the Highest Honor
2002 The Distinguished Doctoral Dissertation Award
2001 Hong Kong Qiu Shi Graduate Scholarship
The Ren laboratory aims to study epigenetic mechanisms under physiological and pathological conditions.
The research in the Ren laboratory is focused on understanding the physicochemical principles that underpin how the gene expression programs are established and maintained under physiological and pathological conditions. We have discovered that epigenetic regulatory complexes phase-separate to assemble liquid droplets that facilitate gene regulation. We have developed and applied in vitro and in vivo single-molecule imaging to address fundamental questions in the epigenetic field. Our research is multidisciplinary across physical and life sciences.
We are working on the following projects:
1. Liquid-liquid phase separation links with the genome organization
How do cells spatially and temporally organize biochemical reactions to achieve functions is a fundamental question in biology. We study the roles of liquid-liquid phase separation of epigenetic regulatory complexes in gene expression programs. We have demonstrated that Polycomb proteins form microscopically visible, liquid-like condensates in cells. These condensates are assembled through liquid-liquid phase separation. These liquid droplets organize chromatin and accelerate the search of Polycomb proteins for their cognate sites.
2. Single-molecule techniques in vitro and in vivo
We have developed and applied innovative single-molecule techniques to address questions of fundamental importance in the epigenetic/chromatin field, indicated by the following. (1) Live-cell single-molecule imaging: The binding and target-search kinetics is essential for understanding how chromatin-binding factors function. My research group developed and applied live-cell single-molecule tracking to quantify binding and target-search kinetics of epigenetic complexes in vivo. (2) Sm-ChIPi: The molecular composition and stoichiometry of epigenetic complexes on chromatin dictates functions of epigenetic complexes. My laboratory developed a new single-molecule chromatin immunoprecipitation imaging (Sm-ChIPi) approach that enables counting the number of epigenetic regulators on chromatin. Sm-ChIPi combines chromatin immunoprecipitation with single-molecule imaging. We use these state-of-the-art single-molecule techniques to address questions of fundamental importance in the epigenetic field that are not easily accessible by classical approaches.
3. Defining the mechanisms underlying diffuse intrinsic pontine gliomas
Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive and difficult to treat brain tumors. DIPGs exhibit a characteristic mutation of lysine 27 to methionine (K27M) in genes encoding histone H3. H3K27 (the native protein) and its modification are the substrate of Polycomb proteins. How the H3K27M mutation affects the functioning of Polycomb remains controversial. By combining live-cell single-molecule imaging and genetic engineering, we have uncovered a novel molecular mechanism underlying the oncogenic H3K27M mutation; it alters the target-search kinetics of Polycomb proteins, which in turn affects their functions. Furthermore, we have pointed out a potential therapeutic target for improvement of DIPG treatment. Our results suggest that the reduced “sampling” frequency of Polycomb proteins for target sites, by prolonging its search process, reprograms the genomic occupancy of Polycomb proteins, which is a new insight into the reprogramming of epigenome by a cancer mutation in vivo.
Prospective students and postdocs
The Ren laboratory is funded by the National Institute of Health (R01s and R03) and the American Cancer Society. We are always looking for students, research assistants, and postdoctoral researchers who are highly motivated and exciting to discover knowledge. If you are interested in our research, please feel free to contact me (firstname.lastname@example.org).
Selected publications since independence
#indicates the corresponding author
Kyle Brown, Samantha Kent, and Xiaojun Ren# (2021) Monitoring Binding and Target-search Dynamics of Epigenetic Regulatory Factors Using Live-Cell Single-Molecule Tracking.
STAR Protocols, 2 (4), 100959
Yi Zhang, Kyle Brown, Yucong Yu, Ziad Ibrahim, Mohamad Zandian, Hongwen Xuan, Steven Ingersoll, Thomas Lee, Christopher C Ebmeier, Jiuyang Liu, Daniel Panne, Xiaobing Shi, Xiaojun Ren, Tatiana G Kutateladze (2021) Nuclear condensates of p300 formed though the structured catalytic core can act as a storage pool of p300 with reduced HAT activity.
Nature Communications Jul 29; 12(1):4618.
Kyle Brown, Haralambos Andrianakos, Steven Ingersoll, Xiaojun Ren# (2021) Single-molecule imaging of epigenetic complexes in living cells: insights from studies on Polycomb group proteins.
Nucleic Acids Research Jul 9; 49(12):6621-6637
Samantha Kent, Kyle Brown, Chou-hsun Yang, Njood Alsaihati, Christina Tian, Haobin Wang, Xiaojun Ren# (2020) Phase-separated Transcriptional Condensates Accelerate Target-search Process Revealed by Live-cell Single-molecule Imaging.
Cell Reports Oct 13; 33: 108248
Yi Zhang, Bianca Bertulat, Adam H. Tencer, Xiaojun Ren, Gregory M. Wright, Joshua Black, M. Cristina Cardoso, Tatiana G. Kutateladze (2019) MORC3 Forms Nuclear Condensates through
iScience Jul 26; 17:182-189
Roubina Tatavosian, Samantha Kent, Kyle Brown, Tingting Yao, Huy Nguyen Duc, Thao Ngoc Huynh, Chao Yu Zhen, Brian Ma, Haobin Wang, Xiaojun Ren# (2019) Nuclear condensates of the Polycomb protein chromobox 2 (CBX2) assemble through phase separation.
Journal of Biological Chemistry Feb 1; 294(5):1451-1463
- The year in the Journal of Biological Chemistry: 2019. The paper was selected to represent the exciting advance in gene regulation in 2019 by the JBC.
- Significant biochemistry papers from 100+ years of JBC. The paper was included in a collection of highlights (total 46 papers) published in the JBC during the last Century and beyond.
Roubina Tatavosian, Huy Nguyen Duc, Thao Ngoc Huynh, Dong Fang, Benjamin Schmitt, Xiaodong Shi, Yiming Deng, Christopher Phiel, Tingting Yao, Zhiguo Zhang, Haobin Wang, Xiaojun Ren# (2018) Live-cell Single-Molecule Dynamics of PcG Proteins Imposed by the DIPG H3.3K27M Mutation.
Nature Communications May 25; 9(1):2080
Roubina Tatavosian, Xiaojun Ren# (2018) Sm-ChIPi: Single-Molecule Chromatin Immunoprecipitation Imaging.
Methods in Molecular Biology 1689:113-126
Huy Nguyen Duc, Xiaojun Ren# (2017) Labelling HaloTag Fusion Proteins with HaloTagLigand in Living Cells.
Bio-protocol Sep 5; 7(17). Pii: e2526
Thao Ngoc Huynh, Xiaojun Ren# (2017) Producing GST-Cbx7 Fusion Proteins from Escherichia coli.
Bio-protocol Jun 20; 7(12). Pii: e2333
Chao Yu Zhen, Roubina Tatavosian, Thao Ngoc Huynh, Huy Nguyen Duc, Raibatak Das, Marko Kokotovic, Jonathan B Grimm, Luke D Lavis, Jun Lee, Frances J Mejia, Yang Li, Tingting Yao, Xiaojun Ren# (2016) Live-cell single-molecule tracking reveals co-recognition of H3K27me3 and DNA targets Polycomb Cbx7-PRC1 to chromatin.
eLIFE Oct 10; 5. Pii: e17667
Roubina Tatavosian, Chao Yu Zhen, Huy Nguyen Duc, Maggie M. Balas, Aaron Johnson, Xiaojun Ren# (2015) Distinct Cellular Assembly Stoichiometry of Polycomb Complexes on Chromatin Revealed by Single-Molecule Chromatin Immunoprecipitation Imaging.
Journal of Biological Chemistry 290(47):28038-54
- The Best of Year Article in Gene Regulation in 2015 by the JBC. The paper was honored to represent the best of year article in gene regulation in 2015 by the JBC.
Roubina Tatavosian, Chao Yu Zhen, Xiaojun Ren# (2015) Single-Molecule Fluorescence Microscopy Methods in Chromatin Biology in Recent Progress in Surface and Colloids Chemistry with Biological Applications (Edited by Chengshan Wang and Roger M. Leblanc). ACS Symposium Series eBooks, Chapter 7, pp 129-136
Colleen M. Bartmana, Jennifer Egelstona, Xiaojun Ren, Raibatak Das, and Christopher J. Phiel A (2015) simple and efficient method for transfecting mouse embryonic stem cells using polyethylenimine.
Experimental Cell Research 330(1):178-85
Chao Yu Zhen, Huy Nguyen Duc, Marko Kokotovic, Christopher Phiel, Xiaojun Ren# (2014) Cbx2 stably associates with mitotic chromosomes via a PRC2 or PRC1-independent mechanism and is needed for recruiting PRC1 complex to mitotic chromosomes.
Molecular Biology of the Cell 25(23):3726-39
Bo Cheng, Xiaojun Ren, Tom K Kerppola (2014) KAP1 represses differentiation-inducible genes in embryonic stem cells through cooperative binding with PRC1 and derepresses pluripotency-associated genes.
Molecular and Cellular Biology 34(11):2075-91
- One of the most read articles in May 2014
CHEM 5810-Graduate Biochemistry I
CHEM 5830-Graduate Biochemistry II
CHEM 4835/5835-Biochemistry of Gene Regulation and Cancer
CHEM 4828-Biochemistry Laboratory
CHEM 5610-Understanding & Presenting Chemical Research
CHEM 3498-Honors Organic Chemistry Lab II