Gene Regulation: Using complex models of a lab-grown retina, researchers at the National Institutes of Health have mapped the 3D organization of genetic material of key embryonic phases of human retinal formation.
The results uncover a very dynamic method by which the architecture of chromatin—the DNA and proteins that make up chromosomes—regulates gene expression and provide a basis for interpreting clinical features in a variety of eye illnesses. Cell Reports published the findings.
Gene Regulation Journey of Retina
The study’s principal investigator, Anand Swaroop, Ph.D., chief of the Neurobiology, Neurodegeneration, and Repair Laboratory at the National Eye Institute (NEI), a division of the National Institutes of Health, said, “These results provide insights into the heritable genetic landscape of the developing human retina, especially for the most abundant cell types that are commonly associated with vision impairment in retinal diseases.”
Gene regulation jounrye of retina: A high-resolution map of the chromatin in a human retinal organoid at five critical developmental stages was produced by the researchers using deep Hi-C sequencing, a technique used to investigate 3D genome organisation. Organoids are lab-grown tissue models designed to mimic the biology and function of a particular kind of tissue in a living organism.
Long strands of DNA are dotted with genes, which are sequences that code for RNA and proteins. These DNA strands are bundled into chromatin fibers, which are subsequently repeatedly looped around histone proteins to create extremely compact structures that can be inserted into the nucleus of a cell.
Millions of contact sites are created by all those loops, where genes come into contact with non-coding DNA sequences that control gene expression, such as silencers, promoters, and super enhancers. These non-coding regions were formerly thought of as “junk DNA,” but it is now understood that they are essential for regulating which genes express themselves and when in a cell. Research on the three-dimensional architecture of chromatin provides insight into how these non-coding regulatory components maintain control over distant genes even when they are located on a DNA strand.
Billions of chromatin contact point pairs were sequenced and analyzed at each of the five major retinal organoid developmental phases.
The results paint a dynamic picture: during retinal development, the nucleus’s spatial arrangement of the genome changes, promoting the expression of particular genes at critical junctures. For example, chromatin contact sites change from a predominantly proximal-enriched condition to add more distal connections during a period when immature cells begin to develop retinal cell features.
The contact point exchanges also seem to be arranged in a hierarchy of compartments. A portion of these compartments, designated “A” and “B,” remain constant while others alternate throughout development, further influencing or suppressing the expression of certain genes.
“The datasets resulting from this research serve as a foundation for future investigations into how non-coding sections of the genome are relevant for understanding divergent phenotypes in single gene mutation (Mendelian) disorders, as well as complex retinal diseases,” Swaroop stated. – GENE REGULATION JOURNEY OF RETINA