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A recent paper in PNAS describes the development of MiniPromoters: human DNA promoters of less than 4 kb, designed to drive gene expression in specific areas of the brain. The initiative is called the Pleiades Promoter Project, and so far they have confirmed brain-region specific activity in knockin mice for 27 of their MiniPromoters. The final goal is to produce 160 fully characterized MiniPromoters to drive gene expression in defined brain regions.The project is a spin-off of the Mouse Atlas Project (hence the name “Pleiades”: in Greek mythology, the Pleiades were the daughters of Atlas). To create the MiniPromoters, the researchers have computationally identified regulatory regions associated with brain-region or cell-type enriched gene expressions. Information about region-specific expression came from the Mouse Atlas Project as well as from the Allen Brain Atlas, which maps the human brain.
Several MiniPromoters driving LacZ in different areas of the mouse brain. (Part of Figure 5 from PNAS paper)
The MiniPromoters are designed to work in both mouse and human brains. While the Pleiades website emphasizes the ultimate goal of selective target delivery in gene therapy, the MiniPromoters can also be used to drive reporter expression in cell types of interest, for example to follow development of particular areas of the brain.
Portales-Casamar, E., Swanson, D., Liu, L., Leeuw, C., Banks, K., Ho Sui, S., Fulton, D., Ali, J., Amirabbasi, M., Arenillas, D., Babyak, N., Black, S., Bonaguro, R., Brauer, E., Candido, T., Castellarin, M., Chen, J., Chen, Y., Cheng, J., Chopra, V., Docking, T., Dreolini, L., D’Souza, C., Flynn, E., Glenn, R., Hatakka, K., Hearty, T., Imanian, B., Jiang, S., Khorasan-zadeh, S., Komljenovic, I., Laprise, S., Liao, N., Lim, J., Lithwick, S., Liu, F., Liu, J., Lu, M., McConechy, M., McLeod, A., Milisavljevic, M., Mis, J., O’Connor, K., Palma, B., Palmquist, D., Schmouth, J., Swanson, M., Tam, B., Ticoll, A., Turner, J., Varhol, R., Vermeulen, J., Watkins, R., Wilson, G., Wong, B., Wong, S., Wong, T., Yang, G., Ypsilanti, A., Jones, S., Holt, R., Goldowitz, D., Wasserman, W., & Simpson, E. (2010). A regulatory toolbox of MiniPromoters to drive selective expression in the brain Proceedings of the National Academy of Sciences, 107 (38), 16589-16594 DOI: 10.1073/pnas.1009158107
D’Souza, C., Chopra, V., Varhol, R., Xie, Y., Bohacec, S., Zhao, Y., Lee, L., Bilenky, M., Portales-Casamar, E., He, A., Wasserman, W., Goldowitz, D., Marra, M., Holt, R., Simpson, E., & Jones, S. (2008). Identification of a set of genes showing regionally enriched expression in the mouse brain BMC Neuroscience, 9 (1) DOI: 10.1186/1471-2202-9-66
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