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Micro- and nanoscale devices for the investigation of epigenetics and chromatin dynamics

Nature Nanotechnology volume 8, pages 709–718 (2013)Cite this article

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Abstract

Deoxyribonucleic acid (DNA) is the blueprint on which life is based and transmitted, but the way in which chromatin — a dynamic complex of nucleic acids and proteins — is packaged and behaves in the cellular nucleus has only begun to be investigated. Epigenetic modifications sit 'on top of' the genome and affect how DNA is compacted into chromatin and transcribed into ribonucleic acid (RNA). The packaging and modifications around the genome have been shown to exert significant influence on cellular behaviour and, in turn, human development and disease. However, conventional techniques for studying epigenetic or conformational modifications of chromosomes have inherent limitations and, therefore, new methods based on micro- and nanoscale devices have been sought. Here, we review the development of these devices and explore their use in the study of DNA modifications, chromatin modifications and higher-order chromatin structures.

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Figure 1: Overview of epigenetic layers and corresponding size scales.
Figure 2: Micro- and nanodevices for mapping DNA covalent modifications.
Figure 3: Micro- and nanodevices for mapping histone modifications and nucleosome arrays.
Figure 4: Micro- and nanodevices for understanding chromatin dynamics and chromosome organization.
Figure 5: Possible hybrid micro- and nanodevice architecture to carry out multiplexed epigenomic measurements from a single cell.

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Acknowledgements

The authors would like to thank R. Karnik, J. Harper, C. Gifford and A. Meissner for discussions, and N. Taylor for assistance with artwork. H.G.C. acknowledges support from the National Institutes of Health grants R01 HG006850-01, U54 CA143876-03 and R01 DA030329-03. C.A.A. acknowledges support from and sponsorship by the Department of the Air Force under Air Force Contract #FA8721-05-C-0002. Opinions, interpretations, recommendations and conclusions are those of the authors and are not necessarily endorsed by the US government.

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  1. Massachusetts Institute of Technology—Lincoln Laboratory, 244 Wood Street, Lexington, 02127, Massachusetts, USA

    Carlos A. Aguilar

  2. School of Applied and Engineering Physics, Cornell University, Ithaca, 14853, New York, USA

    Harold G. Craighead

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Correspondence to Carlos A. Aguilar or Harold G. Craighead.

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H.G.C. is a co-founder of Pacific Biosciences and Odyssey Scientific.

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Aguilar, C., Craighead, H. Micro- and nanoscale devices for the investigation of epigenetics and chromatin dynamics. Nature Nanotech 8, 709–718 (2013). https://doi.org/10.1038/nnano.2013.195

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