Genome-wide Activity and Promoter Status in Stem Cells
Embryonic stem cells (ESC) hold great promise for regenerative medicine due to their ability to differentiate to any type of tissue of the body and to self-renew indefinitely. Global gene expression alterations accompany these dramatic cell fate changes from ESC to differentiated cell or from differentiated cell to induced pluripotent stem cell. Gene expression can be regulated at distinct stages during the transcription cycle; therefore, identifying the rate-limiting step for sets of genes crucial for stem cell pluripotency or lineage specification can reveal critical information about how cell fate changes are initiated.
The focus of this effort is stem cell pluripotency-what triggers it and what sets its tone. The first aim is to map the location, density, and orientation of transcriptionally engaged RNA polymerases in mouse ESC and mouse embryonic fibroblasts (MEF) to gain knowledge of the critical regulatory junctures during transcription for sets of genes turned on in ESC or MEF. We will employ global nuclear run-ons with mass-scale sequencing (GRO-seq) methodology to address this first aim. The next challenge for this effort is to connect a specific rate-limiting step in transcription with a particular factor or structure, which may trigger or reinforce the transcriptional activity and the promoter status of RNA polymerases.
Ultimately, the mechanistic interplay of transcription factors and RNA polymerase II on targeted genes during these cellular transitions is key to our understanding of the basic mechanisms that govern the interplay of pluripotency and differentiation and for exploiting the full potential of stem cells in therapies.Education
- Ph.D. in Genetics (2004), Tufts University School of Medicine, Boston, MA
- M.Phil. in Biological Sciences (1998), Cambridge University, Cambridge, England
- B.Sc. in Biology (1997), Sogang University, Seoul, Korea
- Breault DT, Min IM, Carlone DL, Farilla LG, Ambruzs DM, Henderson DE, Algra S, Montgomery RK, Wagers AJ, Hole N. (2008) “Generation of mTert-GFP mice as a model to identify and study tissue progenitor cells.” Proc Natl Acad Sci U S A. 105(30):10420-5. (PubMed)
- Min IM, Pietramaggiori G, Kim FS, Passegué E, Stevenson KE, Wagers AJ. (2008) “The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells.” Cell Stem Cell. 2(4):380-91. (PubMed)
- Eggan K, Jurga S, Gosden R, Min IM, Wagers AJ. (2006) “Ovulated oocytes in adult mice derive from non-circulating germ cells.” Nature. 441(7097):1109-14. (PubMed)
- Min IM, Selsing E. (2005) “Antibody class switch recombination: roles for switch sequences and mismatch repair proteins.” Adv Immunol. 87:297-328. (PubMed)
- Min IM, Rothlein LR, Schrader CE, Stavnezer J, Selsing E. (2005) “Shifts in targeting of class switch recombination sites in mice that lack mu switch region tandem repeats or Msh2.” J Exp Med. 201(12):1885-90. (PubMed)
- Min IM, Schrader CE, Vardo J, Luby TM, D'Avirro N, Stavnezer J, Selsing E. (2003) “The Smu tandem repeat region is critical for Ig isotype switching in the absence of Msh2.” Immunity. 19(4):515-24. (PubMed)
- Kim T, Kim TY, Song YH, Min IM, Yim J, Kim TK. (1999). “Activation of interferon regulatory factor 3 in response to DNA-damaging agents.” J Biol Chem. 274(43):30686-9. (PubMed)