BBS Faculty Member - Jeannie Lee

Jeannie 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: 19 postdoctoral fellows, 7 graduate students
Visit my lab page here.

Our laboratory uses X-chromosome inactivation (XCI) as a model to study the structure and function of long noncoding RNAs (lncRNA) in epigenetic regulation. 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. Our long-term goal is to understand how lncRNAs interact with chromatin complexes to achieve locus-specific and temporally specific gene expression patterns.

Last Update: 8/22/2013


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.

Lee, J.T. (2009) Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome.
Genes Dev 23, 1831-1842.

Tian, D., Sun, S., and Lee, J.T. (2010) The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation.
Cell 143, 390-403.

Sarma, K., Levasseur, P., Aristarkhov, A., and Lee, J.T. (2010) Locked nucleic acids (LNAs) reveal sequence requirements and kinetics of Xist RNA localization to the X chromosome.
PNAS 107, 22196-201.

Zhao, J., Ohsumi, T.K., Kung, J.T., Ogawa, Y., Grau, D.J., Sarma, K., Song, J.J., Kingston, R.E., Borowsky, M., Lee, J.T. (2010) Genome-wide identification of Polycomb-associated RNAs by RIP-seq.
Mol. Cell 40, 939-953.

Jeon, Y. and Lee, J.T. (2011) YY1 tethers Xist RNA to the inactive X nucleation center.
Cell 146, 119-133.

Yildirim, E., Sadreyev, R.I., Pinter, S.F., Lee, J.T. (2011) X-chromosome hyperactivation in mammals via nonlinear relationships between chromatin states and transcription.
Nat Struct. Mol. Biol. 19, 56-61.

Anguera, M.C., Sadreyev, R., Zhang, Z., Szanto, A., Payer, B., Sheridan, S.D., Kwok, S., Haggarty, S.J., Sur, M., Alvarez, J., Gimelbrant, A., Mitalipova, M., Kirby, J.E., Lee, J.T. (2012) Molecular signatures of human induced pluripotent stem cells highlight sex differences and cancer genes.
Cell Stem Cell 11, 75-90.

† Equal contribution

© 2014 by the President and Fellows of Harvard College