Atlas of non-coding DNA
Researchers from the University of California, San Diego have created a chromatin atlas for the human genome. Chromatin is a complex of DNA and histone proteins in eukaryotic cells; different chromatin configurations of regulatory genes alter the expression of nearby genes. The precise determination of these chromatin fragments in cells of various types of human tissues would be an important step towards understanding the role of regulatory elements of genes (non-coding DNA) in human health or diseases.
The human genome was sequenced 20 years ago, but interpreting this data is still a difficult task. The approximate number of all human genes encoding proteins is known – about 20,000. But this information does not really explain exactly how the cell-building process works and why it is disrupted in diseases. The difficulty lies in the fact that most of the human DNA sequence – more than 98% – does not encode proteins, and it is very difficult to decipher the information embedded in these sequences.
International efforts to study non-coding DNA are reflected in the Encyclopedia of DNA Elements (ENCODE). In particular, the role and functions of chromatin, a complex of DNA and histones that form chromosomes in the nuclei of eukaryotic cells, were studied.
DNA carries the genetic instructions of the cell. Histones are proteins in chromatin that help tightly pack a DNA strand into a compact shape so that it fits in the cell nucleus. Changes in chromatin configuration affect DNA replication and gene expression.
The researchers analyzed more than 600,000 human cells selected from 30 tissue types from several adult donors, then combined this information with similar data from 15 fetal tissue types to determine the chromatin state of approximately 1.2 million cis-regulatory candidate elements in 222 different cell types.
Cis-regulatory elements are regions of non–coding DNA that regulate transcription (copying of a DNA segment into RNA) of neighboring genes. Transcription is the most important process that converts genetic information into action.
Studies conducted in the last decade have established that sequence variations in non-coding DNA are the key driving force of multigenic traits and diseases such as diabetes mellitus, Alzheimer's disease and autoimmune diseases.
The new paradigm, which helps to understand how non-coding genes contribute to diseases, suggests that sequence changes disrupt the function of regulatory elements and lead to impaired gene expression in disease-related cell types, for example, neurons, immune or epithelial cells. However, an obstacle to understanding the function of non-coding risk variants is the lack of a list of regulatory elements specific to different cell types in the human genome.
As a result of this study, cell types corresponding to the signs of the disease were identified for 240 multigenic signs and diseases and the risk of non-coding variants was described.
This resource will greatly facilitate the study of the mechanisms of a wide range of human diseases. The chromatin atlas will also allow the scientific community to identify environmental-specific differences in cell types that are found in several tissues, for example, fibroblasts, immune or epithelial cells.
Article by K.Zhang et al. A single-cell atlas of chromatin accessibility in the human genome.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of UC San Diego: Illuminating Dark Matter in Human DNA.