Health
DNA organization of human retinal cells revealed using 3D maps
Adult human retinal cells are highly specialized sensory neurons. Because they do not divide, they are relatively stable for investigating how the three-dimensional structure of chromatin contributes to the expression of genetic information.
it’s long DNA strand It is wrapped around histone proteins by chromatin filaments, looping repeatedly to produce a very compact structure. All these loops create multiple points of contact where protein-coding gene sequences interact with gene regulatory sequences such as superenhancers, promoters and transcription factors.
These non-coding sequences have long been called “junk DNA”. The specific processes by which noncoding regulatory elements exert control are how these sequences influence which genes are transcribed and when, even when their placement on the DNA strand is distant from the genes they regulate. A recent study has shown that
Researchers at the National Eye Institute used deep Hi-C sequencing, a tool for studying 3D genome organization, to create a high-resolution map containing 704 million contact points within retinal cell chromatin. did.they mapped the organization of human retinal cells chromatinThe resulting comprehensive gene regulatory network describes how genes are commonly regulated and how the retina functions in both uncommon and common eye conditions. clarify what to do.
Anand Swaroop, principal investigator of the study, said: “This is a combination of genetic mutations associated with age-related macular degeneration (AMD) and glaucoma, two leading causes of vision loss and blindness, and retinal regulatory genomics. It’s the first detailed integration of topology.”
The new map contains 704 million contacts. retinal cells chromatin. The map was constructed using postmortem retinal samples from four human donors. Chromatin topological maps were subsequently integrated with datasets on retinal genes and regulatory components. A dynamic picture of interactions within chromatin surfaced, including regions with varying degrees of separation from other regions. DNA Regions and hotspots of gene activity.
They found distinct patterns of interactions in retinal genes, suggesting that the 3D organization of chromatin plays an important role in tissue-specific gene regulation.
Swaroop Said, “Having such high-resolution images of genome structure will continue to provide insight into the genetic control of tissue-specific functions.”
Moreover, similarities in chromatin organization between mice and humans indicate conservation across species, highlighting the importance of chromatin organization patterns for retinal gene regulation. In the human retina, so was her 35.7% of gene pairs that interacted through mouse chromatin loops.
Chromatin topology maps were integrated with information about genetic variants associated with the two most common diseases that cause AMD and glaucoma. decreased vision and blindness. This finding points to specific candidate causative genes involved in these diseases.
An integrated genomic regulatory map can be used to assess genes associated with other common retinal-related diseases such as diabetic retinopathy, determine defective heritability, and correlate genotypes and phenotypes in hereditary retinal and macular diseases. It is also useful for understanding
Journal reference:
- Marchal, C., Singh, N., Bats, Z. et al. High-resolution genomic topology of the human retina reveals super-enhancer-promoter interactions at tissue-specific and multifactorial disease loci. nut common 13, 5827 (2022). Doi: 10.1038/s41467-022-33427-1
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