Question

1. Explain how it is that cells in different parts of the body have the same DNA yet express different genes. Explain using molecular components of gene regulation.

Answer 1

Every cell in the human body shares a common starting point: a fertilized egg. As a result, all of our cells theoretically contain the same DNA — ignoring specific cell types, such as erythrocytes and gametes, and the cumulative effects of DNA changes through mutation and telomere shortening.

The reason is that each cell — whether a neuron, skin cell, or a photoreceptor cell — uses the genes that it has differently. All cells have the same set of genes (~20,000 in humans) but it is up to the individual cell whether each gene is turned on or off.

What is a gene? , it can roughly described as a region of DNA that can undergo transcription to produce a corresponding mRNA intermediate, which can then be translated into a specific protein molecule.

It is actually proteins, not DNA, that determine the activity and function of the cell, so the control of protein expression through regulation of each gene is of fundamental importance. This can occur through one of a several mechanisms:

1. Genetic control: a direct interaction between a proteinaceous transcription factor (TF) and the gene. The TF will bind to the DNA around the gene’s coding region and either enhance or repress its expression.
2. Epigenetics: control of DNA transcription levels which occurs either through changes in the DNA structure (not sequence) or interaction with non-specific DNA binding proteins. In effect, epigenetics is concerned with altering the accessibility of DNA to the transcriptional machinery.
3. Post-transcriptional regulation: modification of the stability, nature and distribution of the mRNA transcripts, which in turn affects the identity and abundance of each protein product.
4. Post-translational regulation: specific control of the final protein product by either chemical modifications, such as phosphorylation or glycosylation, or degradation. Of note is that the TF can also be regulated post-translationally, thus affecting its ability to bind DNA and regulate gene expression.

By either enhancing or repressing the expression of each gene, a cell can become highly specialized. For instance, a neuron has absolutely no need for rhodopsin, a protein involved in light-sensing. In the photoreceptor cells of the retina however, rhodopsin is integral to the cell's function, so its expression will be greatly enhanced. Conversely, neurons require very high expression levels of specific ion channels, such as the voltage-gated ion channel, but these genes will be repressed in photoreceptor cells.

In essence, for each gene in each cell there will be differing levels of expression according to the conditions around the cell, signals received at the cell surface membrane, and the specific cell type (determined during development of the embryo). It is through this process that the function and morphology of each cell is unique.

Regulatable gene expression is why the Human Genome Project (which was undeniably very important) has only provided us with a glimpse into how human biology works. It shows us all of the possible proteins in each cell, but coming to understand the expression patterns of individual proteins in different cells will be fundamental in the decades to come.