Epigenetic Mechanisms of Gene Regulation
One of the fundamental questions in biology aims to understand molecular mechanisms of the control of cellular states. This encompasses the specification of cellular states during embryogenesis, the abnormal transformation of normal cells to cancer cells, and the “forced” induction of somatic cells to pluripotent cells. The establishment and maintenance of specific cellular states require unique transcription programs composed of networks of transcription factors, cofactors and epigenetic regulators. The goal of Dr. Xiaojun Ren laboratory is to understand control mechanisms of cellular states by epigenetic regulation of transcriptional programs.
The current ongoing research topics:
(1) Visualization of cellular PcG epigenetic regulatory complexes on chromatin by single-cell live imaging and single-molecule fluorescence microscopy
Epigenetic regulatory complexes perform cellular functions by acting on chromatin. In vitro biochemical studies have defined certain rules for combinatorial assembly of PcG epigenetic regulatory complexes. It remains, however, unresolved how PcG complexes assemble on chromatin in cellular environments during cell division and differentiation. My laboratory is addressing the challenging questions by advanced imaging techniques including single-cell live imaging (FLIM, FRET, FRAP, FCS/FCCS, and ICS) and single-molecule imaging and using embryonic stem cell as a model system.
(2) Roles of PcG proteins in organization of the genome to high-order chromatin structure
The high-order organization of the genome into chromatin fibers and chromosomes is now known to critically contribute to gene regulation and control of the gene expression program (Tom Misteli, Cold Spring Harb Perspect Biol August 2010; 2:a000794). Although genome-scale mapping chromatin modifications and occupancy of transcription factors and cofactors on chromatin have yielded insights into the question of how genomes actually work in vivo, the mechanisms for the cellular organization of genomes and their impact on genome regulation still remain elusive. My laboratory is developing novel techniques that enable fluorescently labeling specific genes without background, which facilitates to visualize organization of genes at single-molecule level. By doing so, my laboratory will be addressing the roles of PcG epigenetic regulatory complexes in organizing high-order chromatin structures during cellular differentiation and cell cycle progression.
These above topics integrate multiple disciplines and will create a platform for understanding cellular events at the molecular level. The students in the laboratory will have training in a diversity of intellectual and advanced experimental approaches that include biochemistry, biophysics, molecular and cellular biology, stem cell, and epigenetics, and a record of productivity in research. Students interested in the laboratory research are encouraged to contact me via email: XIAOJUN.REN@UCDENVER.EDU.