Profiling of chromatin accessibility and identification of general cis-regulatory mechanisms that control two ocular lens differentiation pathways

Promoters and enhancers are cis-regulatory DNA sequences that control specificity and quantity of transcription. Both are rich on clusters of cis-acting sites that interact with sequence-specific DNA-binding transcription factors (TFs). At the level of chromatin, these regions display increased nuclease sensitivity, reduced nucleosome density, including nucleosome-free regions, and specific combinations of posttranslational modifications of core histone proteins. Together, “open” and “closed” chromatins represent transcriptionally active and repressed states of individual genes, respectively. Cellular differentiation is marked by changes in local chromatin structure. Lens morphogenesis, regulated by TF Pax6, includes differentiation of epithelial precursor cells into lens fibers in parallel with differentiation of epithelial precursors into the mature lens epithelium.

Cellular differentiation is driven by the coordinated expression of batteries of genes that encode proteins required for cellular specialization and function. Differentiation is mostly regulated at the level of transcription. Tissue specificity of transcription is primarily regulated by a combinatorial action of sequence-specific DNA-binding transcription factors and their interactions with promoters and distal enhancers

these studies pave the road for follow-up functional studies to dissect roles of candidate enhancers in temporal and spatial gene regulation during lens development and identification of mutations in noncoding regulatory regions of genes that regulate lens development and when mutated could cause cataracts and other lens abnormalities in humans.