The Telese lab studies how the environment influences brain function in health and disease. We approach this broad question by studying epigenetic modifications that store the molecular responses of a cell to its environment. We focus on epigenetic mechanisms underlying cell-type specific gene expression by using next-generation sequencing techniques in cellular systems or model organisms. The identification and manipulation of epigenetic processes in the brain may enhance our basic understanding of brain function and open the door to new treatments for brain diseases.
One focus of our research is to understand how non-coding enhancer regions of the genome regulate gene expression programs underlying learning and memory. Our experimental approach includes sequencing methodologies and behavioral analysis of genetically engineered mice that enable us to examine enhancer function in distinct neuronal populations, such as excitatory and inhibitory neurons.
Another major focus of the lab is exploring the contribution of epigenetic mechanisms to brain function during adolescence. Adolescence represents a critical time window of neurodevelopment during which the brain undergoes critical changes at the behavioral, cellular and molecular level. The adolescent brain is highly responsive to the environment and this plasticity might lend to this period of development a greater vulnerability to external insults, such as drugs of abuse. We investigate the effects of marijuana on the adolescent brain using novel mice models that permit the analysis of cell-specific epigenetic pathways.
Finally, we are interested in how genetic variants influence behavioral traits through epigenetic regulation of gene transcription.
- Feng Yang, Qi Ma, Zhijie Liu, Wenbo Li, Yuliang Tan, Chunyu Jin, Wubin Ma, Yiren Hu, Jia Shen, Kenneth A. Ohgi,
Francesca Telese, Wen Liu, Michael G. Rosenfeld. “Glucocorticoid Receptor:MegaTrans Switching Mediates Repression of ERα-Regulated Transcriptional Program” Molecular Cell. 66 (3), 321–331 4 May, 2017
Telese F. Keystone Symposia on Neuroepigenetics - Bridging the gap between genome and behavior. Neuroepigenetics (2015). doi: 10.1016/j.nepig.2015.05.001.
- Ma Qi,
Francesca Telese† “Genome-wide epigenetic analysis of MEF2A and MEF2C transcription factors in mouse cortical neurons” (2015) Communicative & Integrative Biology. DOI: 10.1080/19420889.2015.1087624
- Wang J*†,
Telese F*†, Tan Y*, Li W, Jin C, He X, Basnet H, Ma Q, Merkurjev D, Zhu X, Liu Z, Zhang J, Ohgi K, Taylor H, White RR, Tazearslan C, Suh Y, Macfarlan TS, Pfaff SL, Rosenfeld MG†. LSD1n is an H4K20 demethylase regulating memory formation via transcriptional elongation control. Nat Neurosci. 2015 Sep;18(9):1256-64.
- Ryu S.,
Telese F., Russo T., Rosenfeld M.G., Suh Y. “An epigenomic role of Fe65 in the cellular response to DNA damage”. Mut. Res: Fundam. Mol. Mech. Mutagen. (2015). doi:10.1016/j.mrfmmm.2015.01.006
Telese F.*, Gamliel A.*, Krawczyk D.*, Garcia-Bassets I.* and Michael G. Rosenfeld (2013) “Seq-ing Insights into the Epigenetics of Neuronal Gene Regulation” Neuron 77, 77(4):606-2
Telese F.†, Ma Q, Perez PM, Notani D, Oh S, Li W, Comoletti D, Ohgi KA, Taylor H, Rosenfeld MG†,. LRP8-Reelin-regulated Neuronal (LRN) Enhancer Signature Underlying Learning and Memory Formation. Neuron 86, 1–15, May 6, 2015
- Cook P., Ju B.G.,
Telese F., Wang X., Glass C.K. & Rosenfeld M.G. (2009) “Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions” Nature 458, 591-596.
- Garcia-Bassets I., Kwon Y.S.,
Telese F., Prefontaine G., Hutt K., Cheng C.S., Ju B.G., Ohgi K. A., Wang J., Escoubet-Lozach L., Rose D., Glass C.K., Fu X.D. and Rosenfeld M.G. (2007) “Histone methylation-dependent mechanisms impose ligand dependency for gene activation by nuclear receptors.” Cell. 128(3):505-18.
Telese F., Bruni P, Donizetti A, Gianni D, D'Ambrosio C, Scaloni A, Zambrano N, Rosenfeld MG, Russo T. (2005) “Transcription regulation by the adaptor protein Fe65 and the nucleosome assembly factor SET.” EMBO Rep.6(1):77-82.