Unit Three. The Continuity of Life


12. How Genes Work


12.6. Transcription Control in Eukaryotes


The Goals of Gene Expression Are Different in Eukaryotes

In multicellular organisms with relatively constant internal environments, the primary function of gene control in a cell is not to respond to that cell’s immediate environment, like a prokaryote does, but rather to participate in regulating the body as a whole. Some of these changes in gene expression compensate for changes in the physiological condition of the body. Others mediate the decisions that ultimately produce the body, ensuring that the right genes are expressed in the right cells at the right time during development. The growth and development of multicellular organisms entail a long series of biochemical reactions. To produce the necessary enzymes, genes are transcribed in a carefully prescribed order, each for a specified period of time, following a fixed genetic program. The one-time expression of the genes that guide such a program is fundamentally different from the reversible metabolic adjustments prokaryotic cells make to the environment, like the turning on and off of the lac operon. In all multicellular organisms, changes in gene expression within particular cells serve the needs of the whole organism, rather than the survival of individual cells.

The Structure of Chromosomes Can Affect Eukaryotic Gene Expression

The first hurdle faced by RNA polymerase in transcribing a eukaryotic gene is gaining access to it. The DNA of eukaryotes is packaged into chromosomes. The packaging of DNA into nucleosomes and then into higher-order chromosome structures (refer back to figure 8.4) is directly related to the control of gene expression. Chromosome structure at its lowest level is the organization of DNA and histone proteins into nucleosomes, as shown in figure 12.15. These nucleosomes may block binding of RNA polymerase and other proteins called transcription factors at the promoter. The higher-order organization of chromosomes is not completely understood. It involves modifying histones to produce a greater condensation of the chromosomal material, called chromatin, making promoters even less accessible for protein-DNA interactions.



Figure 12.15 DNA coils around histones.

Within chromosomes, DNA is packaged into nucleosomes. In the electron micrograph (top), the DNA is partially unwound, and individual nucleosomes can be seen. In a nucleosome, the DNA double helix coils around a core complex of eight histones; one additional histone binds to the outside of the nucleosome.


DNA Methylation

Chemical methylation of the DNA was once thought to play a major role in regulating gene expression in vertebrate cells. Methylation is the process of adding a methyl group (—CH3) to cytosine nucleotides, creating 5-methylcytosine, which is still able to participate in base pairs. Scientists observed that many inactive mammalian genes are methylated, and it was tempting to conclude that methylation caused the inactivation. However, methylation is now viewed as having a less direct role in transcriptional regulation. It appears instead to block accidental transcription of “turned-off’ genes. DNA methylation thus ensures that once a gene is turned off, it stays off.

Chromatin Structure and Transcriptional Activators

As in prokaryotes, not all gene regulation in eukaryotes involves repression of transcription. In at least some instances, activation of a gene is needed before it can be transcribed. Most activating factors seem to act directly on transcription, helping the RNA polymerase to bind to the promoter. Other “coactivators’ act by modifying the structure of chromatin to make DNA accessible. Recently, some coactivators have been shown to interact with histones. In these cases, it appears that transcription is increased by adding methyl groups to the histones. The methylation of histones disrupts the higher-order chromatin structure, making the DNA more accessible. This control also appears to work in the opposite way, with corepressors having been shown to remove methyl groups from the histones, making the DNA coil more tightly around the histones and restricting access to the DNA.


Key Learning Outcome 12.6. Transcriptional control in eukaryotes can be effected by the tight packaging of DNA into nucleosomes.