Abstract A45: Chromatin dynamics of the zebrafish retina during development and aging

During organogenesis, the retina develops from a single sheet of undifferentiated neuroepithelium into a layered mature tissue composed of Müller, photoreceptor, horizontal, bipolar, amacrine, interplexiform and ganglion cells. This differentiation of various retinal cell types requires the transcription of distinct sets of genes in precise temporal orders. It is unclear how chromatin organization and modifications are specifically regulated at global and regional levels to facilitate the generation of distinct transcriptional profiles required for different retinal cell types. Nor do we know to what extent chromatin structure and organization are altered during retinal aging, or how such alterations lead to unbalanced gene expression profiling and subsequent cell degeneration. In this study, we analyzed the dynamic characteristics of nuclear structures and chromatin organizations of zebrafish retinal cells during development and aging. We show that the degrees of chromatin condensation vary significantly among different retinal cell types, as suggested by varying nuclear volumes and heterochromatin/euchromatin organization. These structural features are altered during the aging process as well. For example, the nuclear volumes of cone photoreceptors increase significantly during aging. The distribution patterns of H3K9me3 and H4K20me3 heterochromatin modifications also vary dramatically among different retinal cell types and at different ages. The gross alterations in nuclear structures and chromatin condensation may suggest extensive changes in gene expression activities. These findings provide insight into how chromatin organization and modifications underlie balanced global transcriptional profiles and consequently, the overall fitness of retinal cells, as well as how such regulations might be altered during the aging process. Our study may have significant social impact because with increasing life expectancy, more and more older people will suffer from age-related macular degeneration and the identification of proper interventions to slow down the retinal aging process would dramatically enhance quality of the life for the elderly. Citation Format: Xiangyun Wei. Chromatin dynamics of the zebrafish retina during development and aging. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A45.