Gene regulation is the process of turning genes on and off. During early development, cells begin to take on specific functions. Gene regulation ensures that the appropriate genes are expressed at the proper times. Gene regulation can also help an organism respond to its environment. Gene regulation is accomplished by a variety of mechanisms including chemically modifying genes and using regulatory proteins to turn genes on or off.
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In the human genome, there are a little less than 20,000 genes. In some cells, many genes are active--say, 10,000--and the other 10,000 would be inactive. In other kinds of cells, maybe the other 10,000 would be active and the first 10,000 would be inactive. And so, gene regulation is the process by which the cell determines which genes will be active and which genes will not be active. And gene regulation is at the bottom of what makes a cell decide to become a red blood cell, or a neuron, or a hepatocyte in the liver, or a muscle cell. So different gene regulation will give you a different program of genes and different genes expressed. There are several different kinds of gene regulation. Some genes, called housekeeping genes, are expressed in almost every cell. And these require a regulatory network or machinery that keeps them on in almost every cell, so these are the enzymes that help make DNA, and perform glycolysis, and burn sugar, and things like that. There are other genes that are called tissue-specific genes. These are genes that, say, would only be expressed in a red blood cell or a neuron. Very often, these genes have transcription factors, which are proteins that bind to DNA, near these genes. And those transcription factors actually help the RNA machinery get there and transcribe that gene in those cells, and those tissues, transcription factors, rather, are expressed specifically in those tissues. There are also factors expressed in those tissues that will be suppressors that can turn a gene off. And then there are genes that are regulated during development. Sometimes they're expressed in fetal life and then turned off in adults, and sometimes it's vice versa. So there are very complex different ways that genes are regulated. I kind of look at it as playing music: You have chords on a guitar, or you play with a right and a left hand on the piano. It depends what strings you push down and what strings you strum, or what keys are up and what keys are down, [that] determine what the profile of the gene expression will be or the sound that you hear.
David M. Bodine, Ph.D.
Chief and Senior Investigator, Genetics and Molecular Biology Branch; Head, Hematopoiesis Section
Dr. Bodine's laboratory investigates the genetics of pluripotent hematopoietic stem cells (PHSCs) to improve the effectiveness of bone marrow transplantation and find better ways to use these unique cells for gene replacement therapy. PHSCs are found mainly in bone marrow. These cells proliferate and differentiate into all the cell types of the peripheral blood. PHSCs also can self-renew without differentiating. A major limitation to bone marrow transplantation is the lack of availability of stem cells. His laboratory seeks to understand and control the self-renewal of PHSCs in order to amplify them, thereby improving stem cell transplantation and gene therapy techniques.