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"The role of long noncoding RNA in epigenomic regulation…"
Professor of Genetics (Pathology), Harvard Medical SchoolMolecular Biologist, Massachusetts General Hospital
Howard Hughes Medical InstituteMassachusetts General HospitalSimches Research Building 185 Cambridge StreetBoston, MA 02114Phone: 617-726-5943Fax: 617-726-6893Email: firstname.lastname@example.org
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.
Eric Aeby, Ph.D.
Rodrigo Aguilar, Ph.D.
Lieselot Carrette, Ph.D.
Hsueh-Ping (Catherine) Chu , Ph.D.
Catherine Cifuentes-Rojas, Ph.D.
Brian Del Rosario , Ph.D.
Teddy Jegu , Ph.D.
Yesu Jeon, Ph.D.
Hungoo Lee, Ph.D.
Hyun Jung Oh , Ph.D.
Michael Rosenberg, Ph.D.
Arneet Saltzman, Ph.D.
Hongjae Sunwoo, Ph.D.
Attila Szanto, M.D., Ph.D.
Chunyao Wei, Ph.D.
Roy Blum, Ph.D.
Barry Kesner, Ph.D.
Derek Lessing, Ph.D.
Chen Yu Wang
Montserrat Michelman, Laboratory Manager
William Press, Research Technician
View all PubMed publications
Sun S, Payer B, Namekawa S, An JY, Press W, Catalan-Dibene J, Sunwoo H, Lee JT. Xist imprinting is promoted by the hemizygous (unpaired) state in the male germ line. Proc Nat Acad Sci USA. 2015; 112(47):14415-22.
Sunwoo H, Wu JY, Lee JT. The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry and suggest a hit-and-run mechanism in mouse cells. Proc Nat Acad Sci, USA. 2015; 112(31):E4216-25.
Minajigi A, Froberg JE, Wei C, Sunwoo H, Kesner B, Colognori D, Lessing D, Payer B, Boukhali M, Haas W, Lee JT. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation. Science. 2015; 349(6245).
Pinter SF, Colognori D, Beliveau BJ, Sadreyev RI, Payer B, Yildirim E, Wu CT, Lee JT. Allelic imbalance is a prevalent and tissue specific feature of the mouse transcriptome. Genetics. 2015; 537-49.
Kung JT, Kesner B, An JY, Ahn JY, Cifuentes-Rojas C, Colognori D, Jeon Y, Szanto A, del Rosario BC, Pinter SF, Erwin JA, Lee JT. Locus-specific targeting to the X chromosome revealed by the RNA interactome of CTCF. Molecular Cell. 2015; 57(2):361-75.
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