In this section, you will explore the following question:
- What is the science of epigenetics and how is this process regulated?
Connection for AP® Courses
One reason that eukaryotic gene expression is more complex than prokaryotic gene expression is because the processes of transcription and translation are physically separated within the eukaryotic cell. Eukaryotic cells also package their genomes in a more sophisticated way compared with prokaryotic cells. Consequently, eukaryotic cells can regulate gene expression at multiple levels, beginning with control of access to DNA. Because genomic DNA is folded around histone proteins to create nucleosome complexes, nucleosomes physically regulate the access of proteins, such as transcription factors and enzymes, to the underlying DNA. Methylation of DNA and histones causes nucleosomes to pack tightly together, preventing transcription factors from binding to the DNA. Methylated nucleosomes contain DNA that is not expressed. On the other hand, histone acetylation results in loose packing of nucleosomes, allowing transcription factors to bind to DNA. Acetylated nucleosomes contain DNA that may be expressed.
Information presented and the examples highlighted in the section support concepts outlined in Big Idea 3 of the AP® Biology Curriculum Framework. The Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP®Biology course, an inquiry-based laboratory experience, instructional activities, and AP® exam questions. A Learning Objective merges required content with one or more of the seven Science Practices.
|Big Idea 3||Living systems store, retrieve, transmit and respond to information essential to life processes.|
|Enduring Understanding 3.B||Expression of genetic information involves cellular and molecular mechanisms.|
|Essential Knowledge||3.B.1 Gene regulation results in differential gene expression, leading to cell specialization.|
|Science Practice||7.1 The student can connect phenomena and models across spatial and temporal scales|
|Learning Objective||3.19 The student is able to describe the connection between the regulation of gene expression and observed differences between individuals in a population|
Epigenetic Control: Regulating Access to Genes within the Chromosome
As stated earlier, one reason why eukaryotic gene expression is more complex than prokaryotic gene expression is because the processes of transcription and translation are physically separated. Unlike prokaryotic cells, eukaryotic cells can regulate gene expression at many different levels. Eukaryotic gene expression begins with control of access to the DNA. This form of regulation, called epigenetic regulation, occurs even before transcription is initiated.
The human genome encodes over 20,000 genes; each of the 23 pairs of human chromosomes encodes thousands of genes. The DNA in the nucleus is precisely wound, folded, and compacted into chromosomes so that it will fit into the nucleus. It is also organized so that specific segments can be accessed as needed by a specific cell type.
The first level of organization, or packing, is the winding of DNA strands around histone proteins. Histones package and order DNA into structural units called nucleosome complexes, which can control the access of proteins to the DNA regions (Figure 16.6a). Under the electron microscope, this winding of DNA around histone proteins to form nucleosomes looks like small beads on a string (Figure 16.6b). These beads (histone proteins) can move along the string (DNA) and change the structure of the molecule.
If DNA encoding a specific gene is to be transcribed into RNA, the nucleosomes surrounding that region of DNA can slide down the DNA to open that specific chromosomal region and allow for the transcriptional machinery (RNA polymerase) to initiate transcription (Figure 16.7). Nucleosomes can move to open the chromosome structure to expose a segment of DNA, but do so in a very controlled manner.
- Methylation of DNA and hypo-acetylation of histones causes the nucleosomes to pack loosely together, inactivating one of the X chromosomes.
- Methylation of histones and hyper-acetylation of DNA causes the nucleosomes to pack tightly together, inactivating one of the X chromosome due to transcriptional repression.
- Methylation of DNA and hypo-acetylation of histones causes the nucleosomes to pack tightly together, inactivating one of the X chromosomes.
- Acetylation of DNA and hyper-methylation of histones causes the nucleosomes to pack tightly together, inactivating one of the X chromosomes.
How the histone proteins move is dependent on signals found on both the histone proteins and on the DNA. These signals are tags added to histone proteins and DNA that tell the histones if a chromosomal region should be open or closed (Figure 16.8 depicts modifications to histone proteins and DNA). These tags are not permanent, but may be added or removed as needed. They are chemical modifications (phosphate, methyl, or acetyl groups) that are attached to specific amino acids in the protein or to the nucleotides of the DNA. The tags do not alter the DNA base sequence, but they do alter how tightly wound the DNA is around the histone proteins. DNA is a negatively charged molecule; therefore, changes in the charge of the histone will change how tightly wound the DNA molecule will be. When unmodified, the histone proteins have a large positive charge; by adding chemical modifications like acetyl groups, the charge becomes less positive.
The DNA molecule itself can also be modified. This occurs within very specific regions called CpG islands. These are stretches with a high frequency of cytosine and guanine dinucleotide DNA pairs (CG) found in the promoter regions of genes. When this configuration exists, the cytosine member of the pair can be methylated (a methyl group is added). This modification changes how the DNA interacts with proteins, including the histone proteins that control access to the region. Highly methylated (hypermethylated) DNA regions with deacetylated histones are tightly coiled and transcriptionally inactive.
This type of gene regulation is called epigenetic regulation. Epigenetic means “around genetics.” The changes that occur to the histone proteins and DNA do not alter the nucleotide sequence and are not permanent. Instead, these changes are temporary (although they often persist through multiple rounds of cell division) and alter the chromosomal structure (open or closed) as needed. A gene can be turned on or off depending upon the location and modifications to the histone proteins and DNA. If a gene is to be transcribed, the histone proteins and DNA are modified surrounding the chromosomal region encoding that gene. This opens the chromosomal region to allow access for RNA polymerase and other proteins, called transcription factors, to bind to the promoter region, located just upstream of the gene, and initiate transcription. If a gene is to remain turned off, or silenced, the histone proteins and DNA have different modifications that signal a closed chromosomal configuration. In this closed configuration, the RNA polymerase and transcription factors do not have access to the DNA and transcription cannot occur (Figure 16.7).
In females, one of the two X chromosomes is inactivated during embryonic development because of epigenetic changes to the chromatin. What impact do you think these changes will have on nucleosome packaging and, consequently, gene expression?
LINK TO LEARNING
View this video that describes how epigenetic regulation controls gene expression.
- Epigenetics would allow new body parts to be synthesized that could replace those damaged by cancer.
- Epigenetics could change the genetic code of all cells in the body to prevent them from becoming cancerous.
- New therapies could be made that changes the genetic code of harmful cancer genes.
- New therapies could be made that do not require altering the cancer cell’s DNA.