GATA-1 – Gene traffic controller
Gene switch will cure anemiaAlexey Tymoshenko, GZT.ru
The search for the reasons why the hemoglobin content in erythrocytes is significantly lower than normal has led scientists to discover a universal mechanism for regulating the work of genes in the cells of the body.
In the future, this discovery may help in the treatment of a number of diseases.
A group of researchers from the University of Pennsylvania and the Children's Hospital of Philadelphia studied the so-called erythroid cells. Oxygen-carrying erythrocytes are formed from these cells. Violations in their formation lead to severe consequences in the form of anemia: tissues stop receiving enough oxygen.
The study of the GATA-1 gene, the activity of which is necessary for the transformation of the "ancestor" of the erythrocyte into a mature cell, allowed not only to advance in understanding the causes of anemia. Scientists have found out that the same gene plays the role of a universal regulator of the work of many other genes, and we are not even talking about dozens or hundreds of genes whose activity level changes due to the intervention of GATA-1. Molecular biologists have found 2616 genes that, in response to the addition of the GATA-1 encoded protein, begin to work either at least twice as actively, or, on the contrary, reduce activity.
(Full text of the article by Yong Cheng et al. Erythroid GATA1 function revealed by genome-wide analysis of transcription factor occupation, histone modifications, and mRNA expression is available in the electronic version of the journal Genome Research – VM.)
The work of genesThe phrase "the work of genes" requires a separate explanation.
The DNA itself, as a rule, is unchanged, and the genes on it remain the same throughout the life of the cell. Each gene encodes an RNA molecule, and when scientists say that "the gene works", it means that at this moment there is a synthesis of RNA encoded by this gene.
Further, RNA molecules either perform some functions inside the cell by themselves, or are sent to ribosomes - cellular "factories" for the production of proteins. Until recently, it was believed that each gene encodes a protein in the end, and because of this, the situation with biological terminology became even more confused: gene and protein began to be designated by the same letters.
The GATA-1 gene turns off 1568 genes. This means that first an RNA molecule is synthesized on the GATA-1 gene matrix, then ribosomes on its basis assemble a protein with the same name GATA-1, and already protein molecules block the synthesis of other proteins in various ways. This whole system of genes, RNA molecules, proteins and countless possible variants of their interaction is extremely confusing, but its study already brings certain practical results.
For example, it is thanks to the ability to navigate the work of genes that scientists can trace the appearance of cancerous tumors. Knowing which gene is "turned on" in tumors, it is possible to create a reliable system for detecting cancer at the earliest stage: the detection of a protein in the blood that encodes the cancer gene – the so-called cancer marker, will be an alarm signal for the doctor.
Autism. Alzheimer's disease. Congenital blindness. Disorders of ovarian development. Arthritis, diabetes, cardiovascular diseases, cancer – almost everywhere scientists need to understand which genes are responsible for a particular process and how exactly the genes interact with each other. Orthopedic traumatologists can use this knowledge to restore bone tissue, dentists will need the ability to reprogram stem cells to grow a new tooth, and psychiatrists will need knowledge of the genetic causes of schizophrenia or depression to find more effective drugs.
Genes. Thousands of them.
The scientists conducted their work on the culture of mouse cells devoid of the GATA-1 gene. Red blood cells from these cells matured only when biologists added a protein encoded by this gene to the culture – and thus the researchers had the opportunity to compare the state of cells before and after exposure to the protein of interest or, ultimately, the gene.
In a living mouse organism, or even more so in a human, such an experiment is impossible: a mouse without GATA-1 would die, and if this gene is not removed, then its initial activity will confuse. Cells were an ideal object, and scientists used them to get information about the activity of 19 thousand genes at once.
The mixture of RNA isolated from cells (the more RNA, the more active the corresponding gene) after special preparation was applied to the so–called gene chips - plates covered with even rows of holes with DNA samples. Where there was a coincidence, a fluorescent label appeared, and a special laser scanner determined which gene was active: tens of thousands of microscopic wells were located on one plate.
Results
The results of scanning the gene chips before and after the addition of GATA-1 were unexpected: scientists came to the conclusion that this gene has an extremely wide spectrum of action. But the study did not end with the conclusion that the gene affects the work of 2616 other genes.
Using a number of additional methods, scientists have found that the genes exposed to GATA-1 are not evenly distributed along the entire length of the DNA molecule. They, as it turned out, are united in groups, separated from each other at the physical level. Researchers believe that we are talking about a new universal mechanism.
In an interview that biologists gave to Science Daily, the authors of the study, however, are still talking about sickle cell anemia. Only in the USA there are over 70 thousand patients whose erythrocytes have an irregular, sickle-shaped shape and tolerate oxygen worse. "If we could turn off the genes that provide this defect and increase the activity of those that lead to the appearance of healthy cells, we could make serious progress in the treatment of diseases," says Ross Garrison, one of the leaders of the study.
Portal "Eternal youth" http://vechnayamolodost.ru24.11.2009