Medical Genetics - V. M. Zaporozhan 2005

Introduction to Medical Genetics
Molecular Basis of Heredity
Regulation of Gene Expression

The Introduction/30.html">Regulation of Gene Expression in Eukaryotes occurs both through a relatively simple principle, where a gene product alters its activity, and through complex mechanisms at the transcriptional and translational levels.

In each Cell of a eukaryotic Organism, only 7–10% of Genes are transcribed. Among them, a group of constitutive, unregulated housekeeping genes stands out; these function throughout the organism's entire life and sustain cellular viability. The second group comprises regulated genes. These are terminal differentiation genes (luxury genes) that function only in specific cell types or at a particular stage of ontogenesis. The activity of these genes depends on both genetic and non-genetic factors. Eukaryotes predominantly exhibit so-called positive Genetic control, in which the major part of The Genome is repressed, and regulation occurs through the activation of required genes. At the transcriptional level, regulation can take place via the following mechanisms:

— gene Amplification (an increase in the number of gene copies);

— binding of regulatory sequences (promoters, enhancers, and silencers) to Proteins known as METABOLISM/31.html">Transcription factors, which either facilitate or hinder transcription;

— the Action of Hormones, which frequently serve as transcription Inducers;

— methylation of DNA NUCLEOTIDES, primarily in GC-rich regions, which prevents the binding of transcription factors and switches off the gene;

— Acetylation of histone proteins, which reduces their binding affinity for DNA and facilitates transcription.

Control at the translational level proceeds through The regulation of mRNA–initiator tRNA–ribosome complex formation, alterations in mRNA lifespan mediated by cytoplasmic factors, and other mechanisms. For instance, in the absence of heme in the Cell Cytoplasm, the synthesis of globin chains ceases, whereas the lifespan of the milk protein casein mRNA increases in the presence of prolactin.

The Regulation of Protein production is also possible by altering the rate and activity of post-translational modifications of the polypeptide chain.

Thus, The formation of any trait cannot be viewed merely as the result of the action of a single pair of allelic genes in the genotype. The expression of the gene responsible for this trait is regulated with the participation of other genes. The term "epigenesis" has been proposed to describe the mechanisms that control Gene Expression without being under its direct control. Examples of epigenetic regulation include the inactivation of one X chromosome in females and The phenomenon of Genomic Imprinting.

Hereditary diseases can be caused not only by alterations in structural genes but also by disruptions in regulatory mechanisms (epigenetic Mutations).