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Xiaojun Ren, Ph.D.

Assistant Professor

Ren

E-mail

Office Location:
SI 4135

Office Hours:
Chem 5810 M/W: 11:45-12:45PM, Chem 4610/5610 F: 12:00-1:00PM, or by appointment

Phone: 303-315-7641

Fax: 303-315-7633

Department of Chemistry »

Expertise Areas:
Stem cells, Epigenetics, Single-molecule imaging

My Addresses:

Mailing Address:
Department of Chemistry
Campus Box 194, P.O. Box 173364
Denver, CO 80217-3364

Physical Location:
Renovated Science Building
1151 Arapahoe Street
Room 3071
Phone: (303) 556-3259
Fax: (303)-556-4776

Research Associate at the HHMI/UM Ann Arbor

Postdoctoral Fellow at the University of Cambridge

Ph.D. in Macromolecular Chemistry and Physics

M.S. in Organic Chemistry

B.Eng. in Polymer Materials Science and Engineering

Laboratory of Single-Cell and Single-Molecule Epigenetics and Chromatin

The Ren lab was set up in September 2012. Since then the lab has been working on pushing the limits of single-molecule fluorescence microscopy methods to study epigenetic regulators in native states and in living cells. The Ren lab is using live-cell single-molecule tracking (SMT) to dissect the chromatin-binding mechanisms of epigenetic factors. The lab developed a new single-molecule chromatin immunoprecipitation imaging (Sm-ChIPi) approach that enables measuring the molecular interactions and stoichiometry of epigenetic regulators at chromatin in cell extracts.

We are working on the following projects:

1. Quantifying chromatin-binding dynamics of epigenetic regulator by single-molecule imaging within living cells

Our lab has been using live-cell single-molecule tracking (SMT) to directly quantify the in vivo chromatin-binding kinetics of epigenetic regulators. The binding dynamics of epigenetic regulators within living cells are highly heterogeneous. Our lab has demonstrated that based on the diffusion coefficients, ultra-sensitive live-cell SMT can discriminate the bound and diffusing molecular populations and to measure their residence times (off-rates). We have used live-cell SMT to unravel a long-standing question about the interactions between chromatin and the Polycomb repressive complex (PRC) 1. By combining live-cell SMT with genetic engineering and site-directed mutagenesis, we have shown that among the Cbx family proteins, H3K27me3 plays a crucial role for Cbx7 and Cbx8 binding, but not other Cbx proteins. We have further demonstrated that the hierarchical cooperation within the Cbx7 protein between the low-affinity H3K27me3-binding module and the high-affinity DNA-binding cassette targets Cbx7 to chromatin, providing a novel example of targeting epigenetic regulators via the integration of genetic DNA and epigenetic modifications.

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 2016 Oct 10;5. pii: e17667 Pubmed/27723458

2. Counting molecular stoichiometry of epigenetic regulator at chromatin by single-molecule imaging

We have developed a novel single-molecule chromatin immunoprecipitation imaging (Sm-ChIPi) to directly study the molecular interactions and stoichiometry of epigenetic regulators at chromatin in cell extracts. We have used Sm-ChIPi to characterize the in vivo molecular interactions and stoichiometry of PRC1 and PRC2 at chromatin and found that one PRC1 associates with seven nucleosomes on average and two PRC2s bind to one nucleosome. These results provide understanding of molecular interactions and assembly of epigenetic regulator at chromatin that approaches to in vivo conditions.            

Roubina Tatavosian, Chao Yu Zhen, Huy Nguyen Duc, Maggie M Balas, Aaron M Johnson, Xiaojun Ren# (2015) Distinct Cellular Assembly Stoichiometry of Polycomb Complexes on Chromatin Revealed by Single-molecule Chromatin Immunoprecipitation Imaging.
J Biol Chem Nov 20; 290(47):28038-54. Pubmed/26381410
(The Best of the Year articles by JBC in 2015)

Roubina Tatavosian, Xiaojun Ren# (2018) Sm-ChIPi: Single-Molecule Chromatin Immunoprecipitation Imaging
Methods in Molecular Biology 2018;1689:113-126

3. Understanding epigenetic inheritance of the transcription program of the cells following mitosis

During mitosis, the chromatin environment dramatically changes, generally leading to the condensation of chromatin, the shutting off transcription and the eviction of most transcription factors from chromatin. Although a subset of transcription factors remains associating with mitotic chromosomes, their binding at mitotic chromosomes is more dynamic than that in interphase. We have used live-cell molecular imaging to quantify the chromatin-binding dynamics of the Cbx-PRC1 complexes during cell cycle. Our results have shown that, among the Cbx family proteins, Cbx2 is the only protein that is entirely enriched and immobilized at mitotic chromosomes, but rapidly exchanges with interphasic chromatin. Interestingly, the mitotic enrichment and immobilization of Cbx2 are independent of PRC1 and PRC2, and mechanistically uncoupled. The unusual dynamic switch of Cbx2 suggests that Cbx2 has potential functional roles in mitosis-related processes, such as mitotic epigenetic inheritance. 

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.
Mol Biol Cell 25:23 3726-3739 Pubmed/25232004

 

We are always looking for students who are highly motivated and exciting to discover knowledge. If you are interested in our research, please feel free to contact me (xiaojun.ren@ucdenver.edu)

The Ren lab has been funded by the National Institute of Health/National Cancer Institute and the American Cancer Society.

Selected publications since independence

#indicates the corresponding author

Roubina Tatavosian, Samantha Kent, Kyle Brown, Tingting Yao, Huy Nguyen Duc, Thao Ngoc HuynhChao Yu ZhenBrian MaHaobin Wang, Xiaojun Ren# (2018) Nuclear condensates of the Polycomb protein chromobox 2 (CBX2) assemble through phase separation
Journal of Biological Chemistry Dec 4. pii: jbc.RA118.006620. doi: 10.1074/jbc.RA118.006620. [Epub ahead of print]

Roubina Tatavosian, Thao Ngoc Huynh, Huy Nguyen Duc, Dong Fang, Benjamin Schmitt, 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 9 (1), 2080

Roubina Tatavosian, Xiaojun Ren# (2018) Sm-ChIPi: Single-Molecule Chromatin Immunoprecipitation Imaging
Methods Mol Biol.1689:113-126

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 the Year article of JBC in Gene Regulation 2015
(http://www.jbc.org/site/bestoftheyear/)
J Biol Chem: Most-Read Full-Text Articles
ASBMB January member news
To hear JBC Podcasts
(https://soundcloud.com/asbmb/jbcpodcast-11-20-15)
Development of new imaging to analyze the binding mechanisms of epigenetic complexes
(http://www.jbc.org/content/290/47/28055.full)

Colleen M. Bartmana, Jennifer Egelstona, Xiaojun Ren, Raibatak Dasa, Christopher J. Phiel (2015) A 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
(*Contributed equally to this work)
One of the most read articles in May, 2014

 

A complete list of publications:
http://www.ncbi.nlm.nih.gov/sites/myncbi/1BEEs8dAp8gAk/bibliograpahy/47366930/public/?sort=date&direction=descending

 

 

 

 

 

 

 

 

 



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