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Insulators and promoters: closer than we think

Abstract

Insulators prevent promiscuous gene regulation by restricting the action of enhancers and silencers. Recent studies have revealed a number of similarities between insulators and promoters, including binding of specific transcription factors, chromatin-modification signatures and localization to specific subnuclear positions. We propose that enhancer-blockers and silencing barrier-insulators might have evolved as specialized derivatives of promoters and that the two types of element use related mechanisms to mediate their distinct functions. These insights can help to reconcile different models of insulator action.

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Figure 1: Chromatin domains and regulatory elements.
Figure 2: Establishment of silencing and barrier activity.
Figure 3: Interactions among enhancers, promoters and enhancer-blocking insulators.
Figure 4: Vertebrate loci at which insulator function is well-studied.
Figure 5: Insulators and three-dimensional organization in the nucleus.

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Acknowledgements

We would like to thank B. Cairns, O. Rando, M. Bulger, D. Clark, G. Hartzog, M. Oki, K. Noma, S. Henikoff, P. Geyer and G. Felsenfeld for comments on an early draft of this Review. We would also like to thank members of the Ro laboratory for comments and criticisms. We apologize for the selective citations, which are a consequence of space limitations. This work was supported by grants from the US National Institutes of Health to R.T.K. (GM078068) and J.R.R (T32-GM008646), and by grant 2008-16 from the GREAT Training Program of the University of California System-wide Biotechnology Research and Education Program to J.R.R.

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Correspondence to Rohinton T. Kamakaka.

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Raab, J., Kamakaka, R. Insulators and promoters: closer than we think. Nat Rev Genet 11, 439–446 (2010). https://doi.org/10.1038/nrg2765

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