Cell differentiation: gene control and regulation
How come all our cells carry the same DNA yet we have varied tissue types and organs?
The scientific way of voicing this question is how cells differentiate: how cells become specialised and have different characteristics? For example, liver cells are different from heart cells.
Before we venture into gene control and regulation, we need to understand how our 2 meters DNA get packed into cells whose diameters do not exceed 6 micrometers. You can imagine this as a 40-kilometre road packed into a tennis ball1! In cells, there are proteins called histones, these are positively charged, they attract the negatively charged DNA, that wrap around the histones. The new structure composed of these histones and the DNA is called chromatin with subunits called nucleosomes. These nucleosomes look like beads on a string, between these beads there are spaces that are 80 nucleotides long.
Figure 1. Nucleosome as a unit. The wrapping of DNA around the 8 histones in a particular way and tightened or kept in place through another histone known as H1.
When the nucleosomes are in the form of an elongated beads on a string, they are accessible for modification but when they are further folded on themselves, access to the DNA or genes are restricted.
Figure 2. DNA from long string to chromosome. The distance between two nucleosome is about 80 nucleotides which folds to form more condensed structure ending in chromosomes. These chromosomes are the most condensed form of DNA.
Genes are subsequences of DNA that encode for RNAs and proteins. RNAs are the messengers of the DNA information to contribute to the production of proteins. Proteins play so many roles in the body such as movement, support, transport, defence, storage, coordination, and receptors to chemical stimuli as well as the enzymes that accelerate the chemical reactions occurring throughout. For example, when genes encoding for receptors are expressed, these receptors are produced. Same happens with other genes for specialised functions.
Figure 3. Packing of DNA to become a chromosome. DNA as a long double helix becomes more condensed by associating with histone proteins which then form the chromatin fibre to finally reach the highest condensed form of the mitotic chromosomes as seen under the microscope.
Three processes have to occur for the cells to become different in shape and function. These processes are cell division, cell differentiation, and morphogenesis. In animals, cells grow in number during the embryonic development and differentiate. These in turn become organised in particular arrangement in the space. Finally, the shape of the animal is determined through the process of morphogenesis (“morph” means shape and “genesis” means creation).
It is important to appreciate that the gene regulation gets is cues from the external and internal environment. External signals, such as hormones, relay information from the external world of the cells instructing nearby cells to change their gene expression. This is how cells arrange themselves to form tissues and organs. Internal indicators depend on how DNA is packed, whether loose or condensed. These cues can then direct which genes are expressed. Genes that are expressed encode for particular proteins which helps with the specialisation of the organs. A typical cell expresses about 20% of its genes. So, the different cell types arise because of the differential gene expression rather than carrying different genes!
Takeaways
DNA becomes condensed to fit in a tiny cell.
Genes in regions of decondensed DNA can be expressed.
Genes that are expressed gives rise to different tissues and organs in an organism.
Uncontrolled gene expression may cause disorders/diseases.
Further explorations
The following YouTube videos are helpful in visualising cell differentiation and DNA packaging:
1. YouTube video by National geographic about a salamander egg differentiating to give rise to a salamander:
2. This video shows the different stages for DNA packaging:
1Alberts B., et al. (2022) Molecular biology of the cell, 7th ed. London: W.W.Norton & company.