7.16 - Hormones and transcription factors

Transcription factors and target genes

The presence of a protein-coding gene in a cell's DNA does not mean that its protein is being produced.

For the gene to be expressed, its DNA must first be transcribed into RNA. In a eukaryotic cell, the RNA is processed to form mature mRNA, which can leave the nucleus and be translated at ribosomes. Controlling transcription therefore controls the supply of messages for protein synthesis.

The protein's three-dimensional structure enables it to interact with a particular DNA sequence. This regulatory sequence is a control site, rather than an instruction for making the transcription factor. A factor may regulate several genes that have suitable control sites; it does not bind indiscriminately to every gene.

The promoter is a DNA region at which the transcription machinery, including RNA polymerase, assembles to begin transcription. Other regulatory sequences can be close to the promoter or farther away. DNA folding can bring a distant bound factor into contact with proteins acting at the promoter. The important link is between a specific regulatory interaction and transcription of its target gene, rather than a rule that every factor sits directly on the coding sequence.

A cell can therefore retain a gene while producing very little of its mRNA. Switching expression changes how the DNA information is used; it does not normally cut out an unwanted gene or change its base sequence.

Activation and repression

DNA-binding transcription factors can increase or decrease transcription, depending on the factor and the regulatory system in which it acts.

An activator binds its regulatory DNA site and helps other proteins assemble or work effectively with RNA polymerase. This increases successful initiation of transcription, producing more RNA from the target gene. After processing, more mRNA can be available for translation.

A repressor reduces transcription. For example, a DNA-bound repressor may interfere with an activator or recruit proteins that make transcription less favourable. Less RNA is produced, so there is less new mRNA available to direct protein synthesis. Removing an activator can also reduce transcription; switching a gene off does not always require adding a new repressor.

Access to DNA also matters. In chromatin, DNA is associated with histone proteins. Some regulatory regions are less accessible because of how the chromatin is packed. Transcription factors can work with proteins that alter chromatin organisation, making relevant DNA more or less accessible to the transcription machinery. This connects transcriptional regulation with the histone modifications studied earlier. It does not mean every transcription factor works only by altering histones, or that accessible DNA must automatically be transcribed.

The consequences in the table assume that other relevant processes, such as mRNA breakdown and translation, do not offset the change. Regulation can involve both activation of some genes and repression of others in the same cell.

The immediate controlled step here is transcription. The factor does not itself translate mRNA or become the protein encoded by its target gene.

Hormone-controlled transcription

A hormone can carry a signal between cells and change the activity of a transcription factor in a target cell.

A hormone is a chemical messenger released by cells and acting on cells with a suitable receptor, a protein that binds the signal. In endocrine signalling, hormones travel in the blood. Receptor compatibility depends on the hormone's molecular structure and the receptor's binding site. Exposure to a hormone alone is insufficient: a cell needs a functional compatible receptor and the machinery needed for the response.

Consider cortisol, a lipid-soluble steroid hormone, as an intracellular-receptor example. Cortisol can cross the cell's phospholipid membrane and bind a glucocorticoid receptor inside the cell. Binding changes the receptor's conformation and activity. The activated hormone–receptor complex can accumulate in the nucleus and regulate target genes.

For an activated target gene, follow the chain:

1. The receptor protein, with hormone bound, acts as a transcription factor and binds an appropriate regulatory DNA sequence.
2. Its interactions with other regulatory proteins help the transcription machinery act at the target gene, increasing transcription. Chromatin accessibility contributes to whether this interaction can occur.
3. More target RNA is made and processed into mRNA. The mRNA reaches ribosomes in the cytoplasm and is translated into protein.
4. The protein changes what the cell can do. For example, if a metabolic enzyme is produced in greater amounts, the cell may have greater capacity for its reaction, provided suitable substrates and conditions are available.