BBS Faculty Member - Jeannie T. Lee

Jeannie T. Lee

Department of Genetics (and Pathology)

Massachusetts General Hospital
Simches Research Ctr., CPZN 6.624
185 Cambridge St.
Boston, MA 02114
Tel: 617-726-5943
Fax: 617-726-6893
Lab Members: 18 postdoctoral fellows, 6 graduate students, 2 research specialists, 2 technical staff
Visit my lab page here.

Our major goal is to understand how lncRNAs interact with chromatin complexes to achieve locus-specific and temporally specific gene expression patterns. We use X-chromosome inactivation (XCI) as a model to study the structure and function of long noncoding RNAs (lncRNA) in epigenetic regulation, and then extend our findings to networks of RNA-protein interactions on a genome-wide scale. Nowhere in the mammalian genome are the abundance and roles of lncRNA more evident than at the X-inactivation center (Xic). This region harbors transcripts that serve as both repressors and activators in the regulation of genes on the X-chromosome. Interestingly, until 150 million years ago, the Xic genes were actually coding and functioned in pathways unrelated to XCI. The replacement of the Xic with noncoding transcripts suggests that lncRNAs may be uniquely suited to some types of epigenetic processes. Our research indicates that two such processes are allelic (cis-regulatory) and locus-specific targeting of chromatin factors (e.g., Polycomb complexes). In addition to pursuing mechanisms of action at the Xic, we are extending analysis to lncRNA occurring on a genome-wide scale and developing novel molecular techniques to do so. We have shown that lncRNAs play a critical role, not only in normal embryonic development, but also in the development of diseases such as cancer. Thus, a major concurrent goal is to leverage the functions of lncRNA to modulate gene expression towards therapeutic purposes. We are especially interested in epigenetic diseases such as Rett Syndrome and cancer.

Last Update: 7/23/2015


For a complete listing of publications click here.



Zhao, J., Sun, B.K., Erwin, J.A., Song, J.J., and Lee, J.T. (2008) Polycomb proteins targeted by a short repeat RNA to the mouse X-chromosome. Science 322, 750-756.

Yildirim, E., Kirby, J.E., Brown, D.E., Mercier, F.E. Sadreyev, R.I., Scadden, D.T., and
Lee, J.T. (2013) Xist RNA is a potent suppressor of hematologic cancer in mice. Cell 152, 727-742.

Sun S, Del Rosario BC, Szanto A, Ogawa Y, Jeon Y, and
Lee JT. (2013). Jpx RNA activates Xist by evicting CTCF. Cell 153, 1537-1551.

Simon, M.D. †*, Pinter, S.F. †, Fang, R. †, Sarma, K., Rutenberg-Schoenberg, M., Bowman, S.K., Kesner, B.A., Maier, V.K., Kingston, R.E.*,
Lee, J.T.* (2013) High-resolution Xist bindings maps reveal 2-step spreading during X-inactivation. Nature 504, 465-469. (†, * equal contribution)

Cifuentes-Rojas, C., Hernandez, A.J., Sarma, K., and
Lee, J.T. (2014) Regulatory interactions between RNA and Polycomb repressive complex 2. Mol Cell. 55, 171-185.

Sarma, K., Cifuentes-Rojas, C., Ergun, A., del Rosario, A., Jeon, Y., White, F. Sadreyev, R., and
Lee, J.T. 2014. ATRX promotes binding of PRC2 to Xist RNA and Polycomb targets. Cell 159, 869-883. PMCID: PMC4379047.

Kung, J.T. †, Kesner, B. †, An, J.Y. †, Ahn, J.Y., Cifentes-Rojas, C., Colognori, D. Jeon, Y. Szanto, A., Del Rosario, B.C., Pinter, S.F., Erwin, J.A., and
Lee, J.T. (2015) Locus-specific targeting to the X chromosome revealed by the RNA interactome of CTCF. Mol Cell 57, 361-375. († equal contribution). PMCID: PMC4316200.

Minajigi, A. †, Froberg, J.E. †, Wei, C., Sunwoo, H., Kesner, B., Colognori, D., Lessing, D., Payer, B. Boukhali, M., Haas, W., and
Lee, J.T. (2015) A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation. Science aab2276, ePub Jun 18. († co-1st authors).

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of Harvard College