This sketch illustrates some of the variability in human cells. The shape and other traits that make each type of cell unique depend mainly on the particular proteins that cell type makes. Proteins are encoded in genes. All the cells in an organism have the same genes, so they all have the genetic instructions for the same proteins. Obviously, different types of cells must use, or express, different genes to make different proteins.
What Is Gene Expression?
Using a gene to make a protein is called gene expression. It includes the synthesis of the protein by the processes of transcription of DNA and translation of mRNA. It may also include further processing of the protein after synthesis.
Gene expression is regulated to ensure that the correct proteins are made when and where they are needed. Regulation may occur at any point in the expression of a gene, from the start of the transcription phase of protein synthesis to the processing of a protein after synthesis occurs. The regulation of transcription is one of the most complicated parts of gene regulation in eukaryotic cells and is the focus of this concept.
Regulation of Transcription
As shown in the figure below, transcription is controlled by regulatory proteins. These proteins bind to regions of DNA, called regulatory elements, which are located near promoters. The promoter is the region of a gene where RNA polymerase binds to initiate transcription of the DNA to mRNA. After regulatory proteins bind to regulatory elements, the proteins can interact with RNA polymerase. Regulatory proteins are typically either activators or repressors. Activators are regulatory proteins that promote transcription by enhancing the interaction of RNA polymerase with the promoter. Repressors are regulatory proteins that prevent transcription by impeding the progress of RNA polymerase along the DNA strand so the DNA cannot be transcribed to mRNA.
An enhancer is a DNA sequence that promotes transcription. Each enhancer is made up of short DNA sequences called distal control elements. Activators bound to the distal control elements interact with mediator proteins and transcription factors. Two different genes may have the same promoter but different distal control elements, enabling differential gene expression.
Although regulatory proteins and elements are typically the key players in the regulation of transcription, other factors may also be involved. For example, regulation of transcription may also involve enhancers. Enhancers are distant regions of DNA that can loop back to interact with a gene's promoter and enhance transcription.
The TATA Box
Different types of cells have unique patterns of regulatory elements that result in only the necessary genes being transcribed. That’s why a blood cell and nerve cell, for example, are so different from each other. However, some regulatory elements are common to virtually all genes, regardless of the cells in which they occur. An example is the TATA box. This is a regulatory element that is part of the promoter of almost every eukaryotic gene. A number of regulatory proteins bind to the TATA box, forming a multi-protein complex. It is only when all of the appropriate proteins are bound to the TATA box that RNA polymerase recognizes the complex and binds to the promoter so transcription can begin.
Regulation During Development
The regulation of gene expression is extremely important during the early development of an organism. Regulatory proteins must turn on certain genes in particular cells at just the right time so the individual develops normal organs and organ systems. Homeobox genes are important genes that regulate development.
Homeobox genes are a large group of similar genes that direct the formation of many body structures during the embryonic stage. In humans, there are an estimated 235 functional homeobox genes. They are present on every chromosome and generally grouped in clusters. Homeobox genes contain instructions for making chains of 60 amino acids called homeodomains. Proteins containing homeodomains are transcription factors that bind to and control the activities of other genes. The homeodomain is the part of the protein that binds to the target gene and controls its expression.
Gene Expression and Cancer
Some types of cancer occur because of mutations in genes that control the cell cycle. Cancer-causing mutations most often occur in two types of regulatory genes, called proto-oncogenes and tumor-suppressor genes. Both are shown in the figure below.
Proto-oncogenes are genes that normally help cells divide. When a proto-oncogene mutates to become an oncogene, it is continuously expressed, even when it is not supposed to be. This is like a car's accelerator pedal being stuck at full throttle. The car keeps racing at top speed. In the case of a cell, the cell keeps dividing out of control, which can lead to cancer.
Tumor suppressor genes are genes that normally slow down or stop cell division. When a mutation occurs in a tumor suppressor gene, it can no longer control cell division. This is like a car without brakes. The car can't be slowed or stopped. In the case of a cell, the cell keeps dividing out of control, which can lead to cancer.
How Cancer Develops. This flow chart shows how a series of mutations in tumor-suppressor genes and proto-oncogenes leads to cancer.
Examples of ways a proto-oncogenes convert into cancer causing genes (oncogenes).
- Using a gene to make a protein is called gene expression. Gene expression is regulated to ensure that the correct proteins are made when and where they are needed. Regulation may occur at any stage of protein synthesis or processing.
- The regulation of transcription is controlled by regulatory proteins that bind to regions of DNA called regulatory elements, which are usually located near promoters. Most regulatory proteins are either activators that promote transcription or repressors that impede transcription.
- A regulatory element that is common to almost all eukaryotic genes is the TATA box. A number of regulatory proteins must bind to the TATA box in the promoter before transcription can proceed.
- The regulation of gene expression is extremely important during the early development of an organism. Homeobox genes, which encode for chains of amino acids called homeodomains, are important genes that regulate development.
- Some types of cancer occur because of mutations in genes that control the cell cycle. Cancer-causing mutations most often occur in two types of regulatory genes, called tumor-suppressor genes and proto-oncogenes.
- Define gene expression.
- Why must gene expression be regulated?
- Explain how regulatory proteins may activate or repress transcription.
- What is the TATA box, and how does it work?
- Describe homeobox genes and their role in the development of an organism.
- Discuss the role of regulatory gene mutations in cancer.
- Explain the relationship between proto-oncogenes and oncogenes.
- If a newly fertilized egg contained a mutation in a homeobox gene, what effect do you think this might have on the developing embryo? Explain your answer.
- Which of the following are proteins?
C. Regulatory elements
D. All of the above
Which of the following is a region of DNA?
C. TATA box
D. Both A and C
Compare and contrast enhancers and activators.
True or False. Mutations in genes that normally either promote or suppress cell division can both cause cancer.
True or False. Gene expression is only regulated at the transcriptional stage.
True or False. If RNA polymerase cannot bind to the promoter of a gene, it cannot transcribe that gene into mRNA.
In order for controlled protein synthesis, genes must be regulated. Take a look here:
Mutations in the regulation of gene expression can lead to uncontrolled cell division, also known as cancer. Learn more here:
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