Background on proteins: The workhorses of the cell
Genes contain the recipes for proteins. Proteins are the true “workhorses” of the cell. Each cell contains an abundance and variety of proteins without which life would be not be possible. Depending on its exact chemical structure and shape, a protein may act as a biological catalyst (called an enzyme), biological signal (such as hormones), energy storage, provide structural integrity to the cell (like the beams in a house), transportation for other compounds (like a taxi or a gate), or have other diverse functions that are essential to life.
Enzymes will be mentioned several times throughout this tutorial, so we will make special mention of them here. Enzymes are compounds that speed up chemical reactions. The words “enzyme” and “protein” are not synonymous. An enzyme is defined by its function and not its chemical makeup, whereas a protein is defined by its chemical makeup and not its function. The vast majority of enzymes are proteins, so when the word “enzyme” is used, you can be almost assured that the enzyme is a protein. However, not all proteins function as enzymes, and not all enzymes are made of protein.
Figure 1. The diagram above contains examples that demonstrate the relationship between enzymes (a functional class) and proteins (a type of chemical). Although almost all enzymes are proteins, not all proteins function as enzymes.
Proteins are made of building blocks called amino acids. Amino acids form chains with each other. These chains are folded in a specific pattern in order to form a precise three-dimensional shape. When an amino acid chain is folded into a three-dimensional shape it is then called a protein. Often, multiple protein subunits (each made from separate amino acid chains) come together to form a protein complex. This partnership is necessary for the protein subunits to complete their true role in the cell. This modular approach to functionality also increases the cell’s flexibility; in some cases, one protein subunit can be swapped out for a slightly different subunit whose function better serves the current situation.
Figure 2. Amino acids are the building blocks of proteins. The image above shows part of the amino acid chain making up a larger protein.
The three-dimensional shape of a protein gives it its identity and helps determine what function it has (enzyme, structural protein, transporter, etc.). In contrast, if amino acid chains are folded incorrectly, the resulting “misfolded” proteins will not perform their intended functions and may instead contribute to the development of diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s.
Proteins are both the end-goal and catalysts of gene expression
Earlier, we said that genes contain the recipes for proteins. Given a little more background, we can now say that a gene contains the instructions for building the particular amino acid chain that is unique to a protein. When a gene is actively signaling a cell to make a certain protein, that gene is said to be expressed. There are three major milestones in gene expression: transcription of DNA to another molecule called RNA, translation to an amino acid chain, and protein folding with modification.
Figure 3. Gene expression begins with DNA and results in protein.
Proteins are the end-product of gene expression, but they also help regulate transcription, translation, and protein folding by acting as enzymes (among other roles). For simplicity, we will describe gene expression as if it were a linear process that begins with DNA and ends with protein. In reality, however, gene expression is part of an enormous, incredibly complex system of feedback loops. Simply put, gene expression produces proteins, which in turn regulate gene expression (sometimes directly and sometimes indirectly).
The first step in gene expression is transcription. When a gene is transcribed, its double-stranded DNA is gently unwound by enzymes. The enzymes read the DNA and transcribe the instructions it contains by producing a new molecule called messenger RNA (mRNA; also called an mRNA transcript). The DNA is then rewound.
Figure 4. During transcription, enzymes read the DNA of a gene and make a copy. The copy is in the form of a new molecule called mRNA.
During gene expression, a single gene may be transcribed repeatedly to produce many mRNA copies. As we will see later in this tutorial series, controlling transcription is at the heart of epigenetics.
Once the DNA has been copied into an mRNA transcript, the instructions in the transcript are then translated into a chain of amino acids by a different enzyme.
Figure 5. During translation an enzyme reads the code in the mRNA transcript and translates it into corresponding amino acids. A chain of amino acids grows out of the enzyme.
Folding and modifications
Amino acid chains have a natural tendency to fold into three-dimensional proteins, but molecular “chaperones” help ensure that the correct shape is achieved in a timely fashion.
Figure 6. A newly-made amino acid chain can fold into a protein on its own, but the assistance of molecular chaperones helps ensure that everything proceeds smoothly and quickly, regardless of other events in the cell that might interfere.
In addition to chaperone-assisted folding, newly-formed proteins may also undergo several kinds of modifications with the help of other molecular machinery. These molecular machines may stabilize the protein’s shape, break off pieces of the protein, or add sugars and other non-protein chemical tags that are meaningful biological signals (these signals may, for example, act like a baggage claim tag, identifying the protein’s final destination inside or outside the cell).
Figure 7. The protein above has undergone several types of modification. It has been cleaved (dotted line), stabilized through bonds (red line), and chemically tagged (green branch).
The cell may modify or not modify its proteins in a particular way depending on other conditions within the body (e.g., in response to something as dramatic as a virus or something as mundane as a hormone signal). The ability to add or remove these modifications helps the cell to build a diverse collection of proteins from a finite and (mostly) unchanging DNA code. This added layer of “customization” is another way in which a cell cultivates versatility. While DNA may be the foundation of a biological system, it is in no way the last word on the subject.
Teaching / Learning Materials
- U. of Utah Genetic Science Learning Center: Epigenetics Multimedia
- NOVA ScienceNow: Epigenetics with Dr. Randy L. Jirtle (Video)
- NHGRI Fact Sheet: Epigenomics
- NCBI Bookshelf: Epigenomics Help – Epigenomics Scientific Background
- Geneimprint: Gateway to gene imprinting information
- EpiGenie Science Writers
- Scitable by Nature Education: Genetics Topic Room
Organizations and Landmark Projects
- International Human Epigenome Consortium
- NIH Roadmap Epigenomics Project
- ENCODE Project: Encyclopedia of DNA Elements
- NHGRI: National Human Genome Research Institute
- NIH Epigenomics Program
- NCHPEG BSSR: Genetics and Social Science – Expanding Transdisciplinary Research
Scholarly Review Articles
- Enivronmental epigenomics and disease susceptibility Jirtle R. and Skinner M., Nat Rev Genet (2007) 8(4):253-62 doi: 10.1038/nrg2045
- Epigenetics, chromatin and genome organization: recent advances from the ENCODE project Siggens L. and Ekwall K., J Intern Med (2014) doi: 10.1111/joim.12231
- Epigenetics as a unifying principle in the aetiology of complex traits and diseases Petronis A., Nature (2010) 465(7299):721-7 doi: 10.1038/nature09230
- Epigenetics and the environmental regulation of the genome and its function Zhang T. and Meaney M., Annu Rev Psychol (2010) 61:439-66 doi: 10.1146/annurev.psych.60.110707.163625
Epigenomic Data: Visualize, Browse, and Download