16.3 Regulation of Eukaryotic Epigenetic Genes - Biology for AP® Courses | OpenStax (2023)

Learning goals

In this section, you will examine the following question:

• What is the science of epigenetics and how is this process regulated?

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One reason eukaryotic gene expression is more complex than prokaryotic gene expression is that the processes of transcription and translation are physically separate within the eukaryotic cell. Eukaryotic cells also package their genomes in a more sophisticated way than prokaryotic cells. Consequently, eukaryotic cells can regulate gene expression at multiple levels, starting with controlling access to DNA. Because genomic DNA folds around histone proteins to form nucleosome complexes, nucleosomes physically regulate the access of proteins, such as transcription factors and enzymes, to the underlying DNA. DNA and histone methylation causes nucleosomes to pack tightly together, preventing transcription factors from binding to DNA. Methylated nucleosomes contain DNA that is not expressed. On the other hand, histone acetylation results in loose nucleosome packing, allowing transcription factors to bind to DNA. Acetylated nucleosomes contain DNA that can be expressed.

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Epigenetic control: regulation of access to genes within chromosomes

As noted above, one of the reasons eukaryotic gene expression is more complex than prokaryotic gene expression is that the processes of transcription and translation are physically separate. Unlike prokaryotic cells, eukaryotic cells can regulate gene expression at many different levels. Eukaryotic gene expression begins with controlling access to DNA. This form of regulation, called epigenetic regulation, takes place even before transcription begins.

The human genome encodes more than 20,000 genes; each of the 23 pairs of human chromosomes codes for thousands of genes. The DNA in the nucleus is precisely coiled, folded, and compressed into chromosomes that fit inside the nucleus. It is also organized so that specific segments can be accessed by a specific cell type when needed.

The first level of organization, or packaging, is the wrapping of DNA strands around histone proteins. Histones package and arrange DNA into structural units called nucleosome complexes that can control protein access to regions of DNA.Figure 16.6A). Under the electron microscope, this winding of DNA around histone proteins to form nucleosomes resembles small beads attached to a thread (Figure 16.6B). These balls (histone proteins) can move along the strand (DNA) and change the structure of the molecule.

Code16.6 DNA folds around histone proteins to (a) form nucleosome complexes. These nucleosomes control the access of proteins to the DNA below. When viewed through an electron microscope (b), nucleosomes look like beads on a string. (credit "micrograph": adapted work by Chris Woodcock)

If the DNA encoding a particular gene needs to be transcribed into RNA, the nucleosomes surrounding that region of DNA can slide down to open up that specific chromosomal region and allow the transcription machinery (RNA polymerase) to begin transcription.Figure 16.7). Nucleosomes can move to open up the chromosome structure and expose a piece of DNA, but they do so in a very controlled way.

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Code16.7 Nucleosomes can slide along DNA. When nucleosomes are close together (above), transcription factors cannot bind and gene expression is turned off. When the nucleosomes are far apart (bottom), the DNA is exposed. Transcription factors can bind, allowing gene expression. Histone and DNA modifications affect nucleosome spacing.

Refers toFigure 16.7

(Video) Gene Regulation and the Order of the Operon

The X chromosome is very large compared to the Y chromosome. Expressing both copies of most of these genes would cause developmental problems. How is this challenge overcome in female mammals?

1. DNA methylation and histone hypoacetylation cause a dense accumulation of nucleosomes, randomly deactivating one of the X chromosomes in each cell.

2. DNA methylation and histone hypoacetylation cause tight nucleosome packing, inactivating the top half of the paternal chromosome and the bottom half of the maternal chromosome.

3. DNA acetylation and histone hypermethylation cause the nucleosome to unwind, randomly deactivating one of the X chromosomes in each cell.

4. DNA acetylation and histone hypermethylation cause the nucleosome to unwind, deactivating only the paternal chromosome.

How histone proteins move depends on signals found on both histone proteins and DNA. These signals are markers added to histone proteins and DNA that tell the histones whether a chromosomal region should be open or closed.Figure 16.8represents modifications in histone proteins and DNA). These tags are not permanent, but can be added or removed as needed. These are chemical modifications (phosphate, methyl or acetyl groups) attached to specific amino acids of proteins or to DNA nucleotides. The tags do not change the base sequence of the DNA, but they do change the tightness with which the DNA is wrapped around the histone proteins. DNA is a negatively charged molecule; therefore, changes in the histone charge will alter the density to which the DNA molecule will be coiled. When unmodified, histone proteins have a large positive charge; By adding chemical modifications, such as acetyl groups, the charge becomes less positive.

The DNA molecule itself can also be modified. This happens within very specific regions called CpG islands. These are high-frequency sections of DNA pairs (CG) of cytosine and guanine dinucleotides located 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 alteration changes the way DNA interacts with proteins, including histone proteins that control access to the region. Highly methylated (hypermethylated) DNA regions with deacetylated histones are tightly coiled and transcriptionally inactive.

Code16.8 Histone proteins and DNA nucleotides can be chemically modified. Modifications affect nucleosome spacing and gene expression. (credit: NIH custom paper)

This type of gene regulation is called epigenetic regulation. Epigenetic means "around genetics". Changes that occur in histone proteins and DNA do not change the nucleotide sequence and are not permanent. Instead, these changes are temporary (although often lasting several rounds of cell division) and alter chromosome structure (open or closed) as needed. A gene can be turned on or off depending on its location and changes to histone proteins and DNA. If a gene is to be transcribed, histone proteins and DNA are modified around the chromosomal region that codes for that gene. This opens up the chromosomal region to access RNA polymerase and other so-called proteinstranscription factors, to bind to the promoter region, located upstream of the gene, and initiate transcription. If a gene is to remain turned off or shut down, the histone proteins and DNA have various modifications that indicate a closed chromosome configuration. In this closed configuration, RNA polymerase and transcription factors cannot access the DNA and transcription cannot take place.Figure 16.7).