Photosensitive protein involved in gene regulation

Although there are about 20000 genes in the human genome, only a small part of them are continuously transcribed and translated This is determined by the state of the cell, which changes at any time The researchers hope to find switches that can quickly control genes to explore gene expression
Researchers at the broad Institute of MIT and Harvard have used a new technology to find a way to quickly start or stop gene expression, which is to irradiate cells with light   The work is based on a technique called photogenetics The principle of photogenetics is that light can change the function of light sensitive proteins Almost at the same time of the emergence of light, light sensitive proteins receive light signals and quickly promote or inhibit gene expression   Silvana Konermann, a graduate student in brain cognition at MIT, said: "gene expression is a fast dynamic process, so far, the methods used to intervene gene expression are all non dynamic If we want to know more about the dynamic changes of gene expression, we must use some dynamic and naturally occurring means consistent with this process to intervene gene expression "
If we can precisely control gene expression and duration, we can understand the function of some specific genes, especially those involved in learning and memory It can also be used in the study of epigenetic modification   The research is now published online in nature, a recently published journal The senior author of the paper is Zhang Feng, an assistant professor at MIT's McGovern Brain Institute and a core member of the broad Institute   Light control switch
The light switch system is composed of several related parts, including the transcription activating factor (Tale), CRY2 (a light sensitive protein) and cib1 (the natural binding protein of CRY2) The DNA binding protein tale combines with DNA in a specific form Tale is integrated with CRY2 When CRY2 encounters light, it changes the structure and combines with cib1 These parts work together to perform the cell's genetic command - to regulate DNA transcription into mRNA   Using this principle, the researchers transformed cib1 into a form that can be combined with another protein to participate in the regulation of gene expression After the light switch system enters the cell, tale binds to the target DNA When the cells are exposed to light, the CRY2 protein binds to cib1, which is originally free in the cells Cib1 carries a gene activating protein that initiates DNA replication or transcription Alternatively, cib1 carries a gene suppressor protein that inhibits DNA replication or transcription   A single light pulse is enough to induce protein binding and initiate DNA replication and transcription The researchers found that a pulse of light about once a minute is the most effective frequency for continuous transcription In addition, after 30 minutes of continuous light pulses, the level of mRNA transcription of the target gene increased significantly, and once the light pulses stopped, the level of mRNA began to decline within about 30 minutes   By studying 30 different genes from neurons cultured in the laboratory and cells from animals, the researchers found that the gene switch system can increase its transcription level   Karl deisseroth, a professor of bioengineering and optogenetics at Stanford University, said that the innovation of the research lies in that its light switch system controls genes not synthesized but taken from cells Based on this technology, we can observe the expression of specific genes at specific time points   Epigenetic modification
Another function of gene expression regulatory switch is to study epigenetic modification An important field of epigenetics is the chemical modification of histones Histones can bind to DNA and control the expression of related genes The researchers found that epigenetic modifications could be altered by the fusion of Tate and histone   Epigenetic modification plays an important role in the process of learning and memory formation, but due to the lack of effective ways to intervene histone modification, this subject has not been further studied The application of the new technology can accurately interfere with the expression of a single gene, thus providing the possibility for the research of this subject   At present, researchers have confirmed that some histone domains can bind to light sensitive proteins, and they are expanding the types of histone modifications that can be applied to gene regulatory systems   "It's very useful to expand the number of controlled epigenetic markers I hope you can use this technology," said mark brightam, a member of the research team