Epigenetic regulatory mechanisms in vertebrate eye development and disease

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.

Conditional knockdown of DNA methyltransferase 1 reveals a key role of retinal pigment epithelium integrity in photoreceptor outer segment morphogenesis

“…Recent studies have begun to define the transcriptional regulatory networks that dictate photoreceptor development and homeostasis (Corbo et al, 2010;Hu et al, 2010;Hao et al, 2012;Hwang et al, 2012). Despite increasing interest in the role of epigenetic mechanisms (Cvekl and Mitton, 2010;Merbs et al, 2012;Nickells and Merbs, 2012;Popova et al, 2012), the role RESEARCH ARTICLE RPE modulates photoreceptor maturation of the epigenome, if any, in establishing retinal cell fate, differentiation and/or homeostasis is yet to be elucidated.…”

Implication of the miR-184 and miR-204 Competitive RNA Network in Control of Mouse Secondary Cataract

“…The corresponding lens opacity results from EMT-associated changes in crystallin proteins, upregulation of cytoskeletal proteins such as α smooth muscle actin (α-SMA) and fibrotic extracellular matrix remodeling (7)(8)(9). In the pursuit of novel prevention and postsurgical therapies, numerous studies have focused on analyzing the etiology of SC formation, looking at the genetic predisposition and epigenetics as well as genomic and proteomic gene expression patterns (5,10,11). To study the detailed mechanism of SC, rodent cataract surgery models were successfully used, with lens epithelial cells undergoing SC during the initial days after lens fiber removal (12)(13)(14).…”

Transcriptional Activity of Neural Retina Leucine Zipper (Nrl) Is Regulated by c-Jun N-Terminal Kinase and Tip60 during Retina Development

“…Precisely regulated photoreceptor gene expression also drives photoreceptor development, in conjunction with intrinsic and extrinsic regulatory factors (6,19,44,56). The intrinsic factors mainly include transcription factors of the homeodomain, nuclear receptors, and basic motif leucine zipper (bZIP) families (7,19,51). Despite recent progress in identifying photoreceptorspecific transcription factors and their roles in photoreceptor subtype determination, little is known about their molecular mechanisms of action.…”