Researching the molecular mechanisms of epigenetic memory

Part of the Department of Cell and Developmental Biology and the Penn Epigenetics Institute.

Affiliated with graduate programs in Cell & Molecular Biology (G&E), Biochemistry and Molecular Biophysics, Genomics and Computational Biology, and Neuroscience

Roberto Bonasio, Ph.D.

Assistant Professor Of Cell And Developmental Biology

Overview

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.

Areas of Research

- Molecular mechanisms of epigenetic memory
- Noncoding RNAs
- Chromatin biochemistry
- Genes and behavior

Education

- Laurea (Biotechnology) University Of Milan, 2000.
- PhD (Immunology) Harvard Medical School, 2006.

Projects

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 changes on 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).

Figure 1

The latter constitute the focus of our current research. A large fraction of the genome is transcribed into noncoding 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. 

Figure 2

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 and computational approaches to study both conventional systems (mammalian cells) and nonconventional model organisms, such as ants, which offer new, unexplored avenues to study epigenetics (Figure 3).

Figure 3

People

Bonasio Lab Team
Ingvarsdottir, Kristin

Kristin Ingvarsdottir, Ph.D.

Postdoctoral Associate
Gospocic, Janko

Janko Gospocic, Ph.D.

Postdoctoral Associate
Sheng, Lihong

Lihong Sheng, Ph.D.

Postdoctoral Associate
Reiner Brodetzki, Tali

Tali Reiner Brodetzki

Postdoctoral Associate
Warneford-Thomson, Robert

Robert Warneford-Thomson

PhD Student (BMB)
Shields, Emily

Emily Shields

PhD Student (GCB)
Petracovici, Ana

Ana Petracovici

PhD student (CAMB/G&E)
Baella, Brigitte

Brigitte Baella

Undergraduate Student
Christopher, Tim

Tim Christopher

Lab Manager

Ten selected publications

Zhang Q*, McKenzie NJ*, Warneford-Thomson R*, Gail EH, Flanigan SF, Owen BM, Lauman R, Levina V, Garcia BA, Schittenhelm RB, Bonasio R, Davidovich C. RNA exploits an exposed regulatory site to inhibit the enzymatic activity of PRC2. Nat Struct Mol Biol 26(3): 237-247, March 2019.

Gospocic J, Shields EJ, Glastad KM, Lin Y, Penick CA, Yan H, Mikheyev AS, Linksvayer TA, Garcia BA, Berger SL, Liebig J, Reinberg D, Bonasio R. The neuropeptide corazonin controls social behavior and caste identity in ants. Cell 170(4): 748-759.e12, Aug 2017.

Yan H, Opachaloemphan C, Mancini G, Yang H, Gallitto M, Mlejnek J, Leibholz A, Haight K, Ghaninia M, Huo L, Perry M, Slone J, Zhou X, Traficante M, Penick CA, Dolezal K, Gokhale K, Stevens K, Fetter-Pruneda I, Bonasio R, Zwiebel LJ, Berger SL, Liebig J, Reinberg D, Desplan C. An engineered orco mutation produces aberrant social behavior and defective neural development in ants. Cell 170(4): 736-747.e9, Aug 2017.

Bose Daniel A, Donahue Greg, Reinberg Danny, Shiekhattar Ramin, Bonasio Roberto, Berger Shelley L. RNA binding to CBP stimulates histone acetylation and transcription. Cell 168(1-2): 135-149.e22, Jan 2017.

Simola DF*, Graham RJ*, Brady CM, Enzmann BL, Desplan C, Ray A, Zwiebel LJ, Bonasio R, Reinberg D, Liebig J, Berger SL. Epigenetic (re)programming of caste-specific behavior in the ant Camponotus floridanus. Science 351(6268): aac6633, Jan 2016.

Kaneko S, Son J, Shen SS, Reinberg D, Bonasio R. PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells. Nature Structural and Molecular Biology 20(11): 1258-64, Nov 2013.

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(5995): 1068-71, Aug 2010.

Bonasio R*, Tu S*, Reinberg D. Molecular signals of epigenetic states. Science 330(6004): 612-6, Oct 2010.


See all publications on Google Scholar

ADDRESS

Perelman School of Medicine
University of Pennsylvania
3400 Civic Center Boulevard
Building 421, Philadelphia, PA 19104