Roberto Bonasio, Ph.D.
3400 Civic Center Boulevard
Philadelphia, PA 19104
Laurea (Biotechnology )
University of Milan, 2000.
Harvard Medical School, 2006.
Description of Research ExpertiseResearch Interests
Molecular mechanisms of epigenetic memory
Keywords: chromatin, noncoding RNAs, epigenetics, Polycomb, ants.
Description of Research
My laboratory studies the molecular mechanisms of epigenetic memory, which are key to a number of biological processes, including embryonic development, cancer, stem cell pluripotency, and brain function.
Epigenetics allows the inheritance of variation (phenotype) without changes in the DNA sequence (genotype). The fact that pluripotent embryonic stem cells, all sharing the same genome, differentiate into hundreds of cell types implies that information about cellular identity and transcriptional states must be stored somewhere within the cell but not in the primary DNA sequence. It has become apparent that this epigenetic information can be encoded in molecular signatures associated with chromatin, the complex of DNA, RNA, and proteins that packages the genome within the eukaryotic nucleus. These signatures include DNA methylation, histone “marks” and variants, higher-order chromatin structures, and chromatin-associated noncoding RNAs (Figure 1).
The latter constitute the focus of our current research. A large fraction of the genome is transcribed into RNAs that, despite lacking protein-coding potential, perform important regulatory functions. Like proteins, RNA molecules can fold into complex tertiary structures with elaborate surfaces and cavities that mediate highly specific molecular interactions and even catalyze biochemical reactions; like DNA, RNA can form Watson–Crick base pairs with other RNAs or with DNA itself (Figure 2). In other words, RNA is fluent in two languages: the elaborate three-dimensional discourse of proteins and the linear genetic code of DNA. Thus, it seems fitting that RNAs may act as a molecular bridge—an epigenetic “translator”—between chromatin-regulating proteins and the genome sequence. Understanding how noncoding RNAs affect the epigenetic states of cells and organisms will provide us with unprecedented access to the regulatory circuitry that makes multicellular life possible.
We and others have discovered that several chromatin-associated protein complexes bind to noncoding RNAs and that these interactions are essential for their proper recruitment and assembly on chromatin, but we have only scratched the surface of the intricate network of protein–RNA interactions in the nucleus and many questions on how noncoding RNAs regulate epigenetic processes at the molecular, cellular, and organismal level remain unanswered.
We approach these fundamental biological questions from both a mechanistic and a systems-level perspective. We combine traditional biochemistry and molecular biology with genome-wide approaches and computational biology and study both conventional systems (mammalian cells) and nonconventional model organisms, such as ants, which offer new, unexplored avenues to study epigenetics (Figure 3).
Kristin Ingvarsdottir, Ph.D. – Postdoctoral Associate
Tim Christopher – Lab Manager
Chonsheng He — Postdoctoral Associate
Selected PublicationsBonasio R*, Lecona E*, Narendra V, Voigt P, Parisi F, Kluger Y, Reinberg D.: Interactions with RNA direct the Polycomb group protein SCML2 to chromatin where it represses target genes. eLife 3: e02637, Jul 2014.
Kaneko S*, Bonasio R*, Saldaña-Meyer R, Yoshida T, Son J, Nishino K, Umezawa A, Reinberg D: JARID2 regulates recruitment of PRC2 by interacting with noncoding RNAs in embryonic stem cells Molecular Cell 53(2): 290-300, Jan 2014.
Kaneko S, Son J, Shen SS, Reinberg D†, Bonasio R†. : PRC2 binds active promoters and contacts nascent RNA in embryonic stem cells. Nature Structural and Molecular Biology Nov 2013.
Bonasio R*, Li Q*, Lian J, Mutti NS, Jin L, Zhao H, Zhang P, Wen P, Xiang H, Ding Y, Jin Z, Shen SS, Wang Z, Wang W, Wang J, Berger SL, Liebig J, Zhang G, Reinberg D.: Genome-wide and caste-specific DNA methylomes of the ants Camponotus floridanus and Harpegnathos saltator. Current Biology 22: 1755–64, Oct 2012.
Bonasio R.: Emerging topics in epigenetics: ants, brains, and non-coding RNAs Annals of the New York Academy of Sciences 1260: 14-23, Jul 2012.
Gao Z*, Zhang J*, Bonasio R, Strino F, Sawai A, Parisi F, Kluger Y, Reinberg D.: PCGF homologs and RYBP define functionally distinct PRC1 family complexes Molecular Cell 45: 344–56, Feb 2012.
Sims RJ*, Rojas LA*, Beck D, Bonasio R, Schüller R, Drury WJ, Eick D, Reinberg D: The C-terminal domain of RNA polymerase I is modified by site-specific methylation. Science 332: 99-103, Apr 2011.
Bonasio R*, Tu S*, Reinberg D: Molecular signals of epigenetic states. Science 330: 612-6, Oct 2010.
Bonasio R*, Zhang G*, Ye C*, Mutti NS*, Fang X*, Qin N*, Donahue G, Yang P, Li Q, Li C, Zhang P, Huang Z, Berger SL, Reinberg D, Wang J, Liebig J: Genomic comparison of the ants Camponotus floridanus and Harpegnathos saltator. Science 329: 1068-71, Aug 2010.
Bonasio R, Lecona E, Reinberg D: MBT domain proteins in development and disease. Seminars in Cell & Developmental Biology 21: 221-30, Apr 2010.