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Epigenetic Mechanisms of Rubinstein–Taybi Syndrome

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Abstract

Rubinstein–Taybi syndrome (RTS) is an incurable genetic disorder with combination of mental retardation and physical features including broad thumbs and toes, craniofacial abnormalities, and growth deficiency. While the autosomal dominant mode of transmission is limitedly known, the majority of cases are attributable to de novo mutations in RTS. The first identified gene associated with RTS is CREB-binding protein (CREBBP/CBP). Alterations of the epigenetic ‘histone code’ due to dysfunction of the CBP histone acetyltransferase activity deregulate gene transcriptions that are prominently linked to RTS pathogenesis. In this review, we discuss how CBP mutation contributes to modifications of histone and how histone deacetylase inhibitors are therapeutically applicable to epigenetic conditioning in RTS. Since most genetic mutations are irreversible and therapeutic approaches are limited, therapeutic targeting of reversible epigenetic components altered in RTS may be an ideal strategy. Expeditious further study on the role of the epigenetic mechanisms in RTS is encouraged to identify novel epigenetic markers and therapeutic targets to treat RTS.

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Acknowledgments

This study was supported by NIH NS 067283 (H.R.) and Brain Science Flagship Grant (2E24380) (H.R.) from Korea Institute of Science and Technology (KIST).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, Boston University School of Medicine, Boston, MA, 02118, USA

    Elizabeth Park, Hyun Ryu, Neil W. Kowall, Junghee Lee & Hoon Ryu

  2. Boston University Alzheimer’s Disease Center, Boston, MA, 02118, USA

    Elizabeth Park, Hyun Ryu, Neil W. Kowall, Junghee Lee & Hoon Ryu

  3. Department of Neurology, VA Boston Healthcare System, Building 1A, Rm 109, Boston, MA, 02130, USA

    Neil W. Kowall, Junghee Lee & Hoon Ryu

  4. Laboratory for Neuronal Gene Regulation and Epigenetics, Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, Seoul, 110-799, South Korea

    Yunha Kim & Hoon Ryu

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  1. Elizabeth Park
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Correspondence to Hoon Ryu.

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Elizabeth Park and Yunha Kim have equally contributed to this work.

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Park, E., Kim, Y., Ryu, H. et al. Epigenetic Mechanisms of Rubinstein–Taybi Syndrome. Neuromol Med 16, 16–24 (2014). https://doi.org/10.1007/s12017-013-8285-3

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