A research group at the University of Helsinki has discovered the logic that regulates gene regulation in human cells. In the future, this new knowledge could be used to investigate cancer and other genetic disorders.
The DNA of the human genome contains genes that encode proteins. Muscle cells Their strength and brain cells are the ability to process information. DNA also contains genes Regulatory factors It determines when and where the gene is expressed and ensures that the muscle gene is expressed in the muscle and the brain gene is expressed in the brain.
However, the regulatory code that determines gene activity remains poorly understood. The human genome is composed of about 3 billion base pairs, but the genome sequence alone is too short to learn the gene regulation code. The problem is similar to the problem faced by linguists trying to understand a forgotten language based on a few short texts.
Professor Yusshitai Pare’s research group at the Center for Tumor Genetics Research at the Academy of Finland has found a way around this problem to resolve the regulatory code.
New research recently Nature Genetics journal.
“We measured gene regulatory activity from a collection of DNA sequences 100 times larger than the whole. Human genome“. Biswajyoti Sahu, a researcher at the Academy of Finland, who is the lead author of this study, said.
“Instead of using nature Genome sequence, Introduced a random synthetic DNA sequence into human cells. Next, the cells themselves were able to read the new DNA and highlight the sequences that act as active regulators, “Sahu adds, explaining the innovative approach.
Researchers identify key atomic units of gene expression
Researchers have created extensive data sets using a technique known as the massively parallel reporter assay. With this technique, the regulatory activity of millions of DNA sequences can be studied simultaneously in one large assay. The data was analyzed using artificial intelligence tools.
Gene expression is regulated by proteins known as transcription factors that bind to DNA. Researchers have found that the very short DNA sequences to which these factors bind constitute important atomic units of gene expression. Individual transcription factors contribute additively to gene regulation. In other words, each factor independently increases regulatory activity without specific interaction with other factors. In addition, transcription factors may have several parallel functions in the gene regulatory process, such as improving gene expression rates and defining the location of the genome where transcription begins.
“Transcription factor binding motifs can be thought of as words that together define a cell’s genes. Regulation code“Professor Jussi Taipale explains.
Researchers have found that the grammar of the code is relatively weak and that most words can be placed in almost any order without changing their meaning.
“But sometimes it resembles a compound word, but the grammar is powerful and certain combinations of factors need to bind in a particular order to activate gene expression,” says Taipale. increase.
Only a handful of highly active transcription factors in the cell
The researchers compared three different human cell types: colon cancer cells and liver cancer cells, and normal cells from the retina. They found that only a handful of transcription factors were very active in cells.In addition, most Transcription Factor activity is similar regardless of cell type.
Result is, Human cells It can be categorized into different types based on the chromatin context, which is either in a closed chromatin region where the DNA is tightly packed, or in a more open chromatin environment where the DNA is not tightly packed around the histone protein.
Traditionally, the active regulatory element has been thought to be within the open chromatin region, where DNA is easily accessible. Transcription factor.. Therefore, the discovery of active regulatory elements that function within the closed chromatin region is one of the central new observations of the study. In addition, researchers have identified chromatin-dependent regulatory factors. These elements are active at normal sites in the genome, but when they are removed from their original location and moved closer to another gene, their activity is significantly reduced.
Biswajyoti Sahu et al, Sequencing Factor for Human Gene Regulatory Elements, Nature Genetics (2022). DOI: 10.1038 / s41588-021-01009-4
University of Helsinki
Quote: Human gene regulation obtained on February 21, 2022 from https: //phys.org/news/2022-02-uncovers-grammar-human-gene.html by a study (February 21, 2022) The “grammar” behind is revealed.
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Research reveals the “grammar” behind human gene regulation
Source link Research reveals the “grammar” behind human gene regulation