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Yan N, Cheng L, Cho K, et al. Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1. Sci Rep. 2016;6:33887doi: 10.1038/srep33887.
Yan, N., Cheng, L., Cho, K., Malik, M. T., Xiao, L., Guo, C., Yu, H., Zhu, R., Rao, R. C., & Chen, D. F. (2016). Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1. Scientific reports, 633887. https://doi.org/10.1038/srep33887
Yan, Naihong, et al. "Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1." Scientific reports vol. 6 (2016): 33887. doi: https://doi.org/10.1038/srep33887
Yan N, Cheng L, Cho K, Malik MT, Xiao L, Guo C, Yu H, Zhu R, Rao RC, Chen DF. Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1. Sci Rep. 2016 Sep 28;6:33887. doi: 10.1038/srep33887. PMID: 27677711; PMCID: PMC5039414.
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Sci Rep. 2016 Sep 28;6:33887. doi: 10.1038/srep33887.

Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1.

Scientific reports

Naihong Yan, Lin Cheng, Kinsang Cho, Muhammad Taimur A Malik, Lirong Xiao, Chenying Guo, Honghua Yu, Ruilin Zhu, Rajesh C Rao, Dong Feng Chen

Affiliations

  1. Department of Ophthalmology and Ophthalmic Laboratories, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
  2. Schepens Eye Research Institute, Massachusetts Eye &Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
  3. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 54 South Xianlie Road, Guangzhou, Guangdong, P. R. China.
  4. Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, Comprehensive Cancer Center, Department of Pathology, University of Michigan Ann Arbor, Michigan, USA.
  5. Division of Ophthalmology, Surgical Service, Veterans Administration Ann Arbor Healthcare System, Ann Arbor, Michigan, USA.
  6. Veterans Administration Boston Healthcare System, Boston, Massachusetts, USA.

PMID: 27677711 PMCID: PMC5039414 DOI: 10.1038/srep33887

Abstract

Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 million individuals worldwide, but ∼50% do not have a known mutation, implicating contributions of epigenetic factors. We found that embryonic deletion of the histone methyltransferase (HMT) Ezh2 from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of Six1 and its targets. Forced expression of Six1 in the postnatal retina was sufficient to induce photoreceptor degeneration. Ezh2, although enriched in the embryonic retina, was not present in the mature retina; these data reveal an Ezh2-mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy.

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