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Recent Advances in Approaches to the Study of Gene Locus Control Regions

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New Frontiers of Multidisciplinary Research in STEAM-H (Science, Technology, Engineering, Agriculture, Mathematics, and Health)

Part of the book series: Springer Proceedings in Mathematics & Statistics ((PROMS,volume 90))

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Abstract

In the many decades of investigation into the regulation of gene transcription in vertebrates, the locus control region (LCR) has emerged as perhaps the most powerful cis-acting regulatory DNA element that one can envision. An LCR element is unique in that it supports both specific spatiotemporal regulation of transcription during development, and a poorly understood “insulation capacity” that prevents genomic interference with the gene regulatory program it would impose upon a linked transgene. As such, it represents a complete, compact and portable package of the DNA sequence information required to establish an independently and predictably regulated gene locus in native chromatin of a whole animal. Both in vivo and cell culture models have contributed significantly to building the field of LCRs. Nevertheless, the gold standard experimental approach to LCR study is transgenic mice, which has been dominant in the progress made in the field over the past 25 years. However, recent technological advances are resulting in a re-emergence of cell culture based approaches to LCR study, portending a coming era of more rapid progress in this significant but understudied field. The investigation of the unique and powerful gene regulatory activities supported by LCR elements offers unparalleled opportunities to gain insight into cis-mediated transcriptional regulation at the single gene locus level. Furthermore, such insights are critical to advancing the safety and efficacy of gene therapy.

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Acknowledgments

The author thanks D. Loayza, J. Lovett, M. Kučerová-Levisohn and G.D. Raghupathy for helpful comments on the manuscript and A. Lahiji for the digital artwork in Figs. 1 and 2. Research in the author’s laboratory is funded by National Institutes of Health (NIH) grant SC1-GM095402. The research infrastructure of Hunter College is supported in part by NIH grant MD007599.

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  1. Department of Biological Sciences, City University of New York, Hunter College and Graduate Center, 695 Park Avenue, Room 927 N, New York, NY, 10065, USA

    Benjamin D. Ortiz

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Correspondence to Benjamin D. Ortiz .

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  1. Dept of Mathematics & Computer Sciences, Virginia State University, Petersburg, Virginia, USA

    Bourama Toni

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Ortiz, B.D. (2014). Recent Advances in Approaches to the Study of Gene Locus Control Regions. In: Toni, B. (eds) New Frontiers of Multidisciplinary Research in STEAM-H (Science, Technology, Engineering, Agriculture, Mathematics, and Health). Springer Proceedings in Mathematics & Statistics, vol 90. Springer, Cham. https://doi.org/10.1007/978-3-319-07755-0_9

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