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脊椎动物眼发育和疾病中的表观遗传调控机制。

Epigenetic regulatory mechanisms in vertebrate eye development and disease.

机构信息

Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY, USA.

出版信息

Heredity (Edinb). 2010 Jul;105(1):135-51. doi: 10.1038/hdy.2010.16. Epub 2010 Feb 24.

Abstract

Eukaryotic DNA is organized as a nucleoprotein polymer termed chromatin with nucleosomes serving as its repetitive architectural units. Cellular differentiation is a dynamic process driven by activation and repression of specific sets of genes, partitioning the genome into transcriptionally active and inactive chromatin domains. Chromatin architecture at individual genes/loci may remain stable through cell divisions, from a single mother cell to its progeny during mitosis, and represents an example of epigenetic phenomena. Epigenetics refers to heritable changes caused by mechanisms distinct from the primary DNA sequence. Recent studies have shown a number of links between chromatin structure, gene expression, extracellular signaling, and cellular differentiation during eye development. This review summarizes recent advances in this field, and the relationship between sequence-specific DNA-binding transcription factors and their roles in recruitment of chromatin remodeling enzymes. In addition, lens and retinal differentiation is accompanied by specific changes in the nucleolar organization, expression of non-coding RNAs, and DNA methylation. Epigenetic regulatory mechanisms in ocular tissues represent exciting areas of research that have opened new avenues for understanding normal eye development, inherited eye diseases and eye diseases related to aging and the environment.

摘要

真核生物 DNA 以核小体为重复结构单元,组成核蛋白聚合物,即染色质。细胞分化是一个由特定基因的激活和抑制驱动的动态过程,将基因组分割为转录活跃和非活跃的染色质区域。个别基因/基因座的染色质结构在细胞分裂过程中可能保持稳定,从有丝分裂中的单个母细胞到其后代,这代表了表观遗传现象的一个例子。表观遗传学是指由不同于主要 DNA 序列的机制引起的可遗传变化。最近的研究表明,在眼睛发育过程中,染色质结构、基因表达、细胞外信号和细胞分化之间存在多种联系。本综述总结了该领域的最新进展,以及序列特异性 DNA 结合转录因子与其招募染色质重塑酶的作用之间的关系。此外,晶状体和视网膜的分化伴随着核仁组织、非编码 RNA 的表达和 DNA 甲基化的特定变化。眼组织中的表观遗传调控机制是令人兴奋的研究领域,为理解正常眼睛发育、遗传性眼病以及与衰老和环境相关的眼病开辟了新的途径。

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