The expression of genes within the human genome is controlled by a number of different mechanisms. Promoters, enhancers and silencers are segments of DNA that regulate the rate and amount of transcription, or expression, of nearby genes. Transcription is the process of synthesizing RNA as a messenger in order to implement the instructions encoded within DNA. Promoters are generally located immediately upstream from the first exon (coding segment of DNA) of a gene. Enhancers are genetic elements that increase transcription of associated genes. Silencers are genetic elements that suppress transcription of associated genes. Enhancers and silencers can be located some distance away from a promoter, may be upstream or downstream of the promoter on which they act, and can be effective even at considerable genetic distances.

Methylation is another mechanism of gene regulation. In methylation, portions of the DNA molecule, particularly regions of the DNA that control transcription are chemically modified through the action of enzymes called DNA methyltransferases. DNA methyltransferases attach a methyl group (CH₃) to the 5^th position carbon of cytosine bases, typically when cytosines occur in the context of C-G dinucleotides, sometimes referred to as CpG islands. Methylation of DNA usually results in the silencing or suppression of gene expression. Alternatively, a lack of methylation is usually associated with an active state of gene expression. Methylation is crucial for the regulation of gene expression and control of cellular growth throughout life, from embryonic development to adulthood. Methylation also is crucial for X-chromosome inactivation and imprinting.

Imprinting is a form of gene silencing whereby individual genes or groups of genes are methylated during gametogenesis to impart parent of origin effects on gene expression. For example, if a gene is maternally imprinted, (that is silenced in the maternal copy during female gametogenesis) only the paternal copy of the gene is expressed in the child. Paternal imprinting of genes also occurs. During gametogenesis, parental imprints are erased and reset in a manner consistent with whether the gametogenesis is occurring in a male or a female. A number of human genetic diseases occur because of mutations in imprinted genes or in the genetic control sequences responsible for setting, resetting or controlling imprinted regions. Such diseases include Angelman syndrome and Prader-Willi syndrome, which occur because of mutations in imprinted genes or errors in imprinting of genes on chromosome 15. These disorders also can be caused when errors in mitosis or meiosis produce a child who inherits both copies of his or her chromosome 15 from a single parent, resulting in inheritance of only imprinted copies of the genes involved and no active copy. This phenomenon is called uniparental disomy, or UPD.

Another type of genetic regulation is exerted at the level of RNA processing through a mechanism called alternative splicing. In alternative splicing, certain exons (coding segments of DNA) of a gene may be alternately included in the final mRNA product. In this way, inclusion of particular exons only in certain tissues or only at certain times during development permits cells to modify the performance characteristics of a particular protein, thereby altering the function or effect of a protein in a cell or tissue. As shown in the graphic, this precursor RNA is alternatively spliced into 3 different isoforms. Isoform 1 contains all 4 exons; isoform 2 contains only exons 1, 2, and 4; and, isoform 3 contains only exons 1 and 4.

Various factors, including DNA sequences, also contribute to the rate of production and stability of mRNAs. By controlling the rate at which new mRNAs are transcribed from a particular gene and the decay kinetics of a mRNA (the rate at which a mRNA is degraded within a cell), cells exert control over the amount of protein that is made from an mRNA, thereby influencing the level of particular proteins within cells and tissues. Different mRNAs have different decay kinetics, meaning that some are degraded very quickly and others are degraded much more slowly. For example, the mRNAs of many cellular growth factors and transcription factors are degraded very quickly, resulting in tight control of the temporal aspects of their cellular signaling properties. On the other hand, mRNAs that encode enzymes can be much longer lived.

During X-inactivation, most genes on one of the X chromosomes of a female are inactivated in a mechanism that provides dosage compensation to equalize the level of gene expression of most X-linked genes in females to that of males who have only one X chromosome. This process, often called Lyonization, results in the formation of a Barr body, the highly compacted, inactive X chromosome. In the photograph, Barr bodies are shown by arrows. The form of DNA in the inactive X-chromosome is called heterochromatin.

In human females, one X chromosome or the other is inactivated in each cell early in development. As a result, some human female cells have one X chromosome active, while the rest of the cells have the other X chromosome active. Typically, X-inactivation is random, or near random, meaning that roughly half of a female's cells express the genes of one X chromosome and the other half of her cells express genes from the other X chromosome. However, in some females, X-inactivation is not random, but skewed. In cases of nonrandom, or skewed X-inactivation, all or most cells of a female express X-linked genes from a single X chromosome. In reality, nonrandom X-inactivation may be less representative of the process of X-inactivation than of reduced survival of cells with a particular X chromosome inactivated, making it appear that X-inactivation was nonrandom.

In some cases, females who carry X-linked genetic diseases can be affected by those diseases, if X-inactivation is not random. For example, if a structural abnormality disrupts the pattern of X-inactivation, then most or all of a female's cells will express genes from a single X chromosome. If there are genes that are disrupted by the structural abnormality, and those genes cause a disorder, the female can show symptoms of the disorder. For many X-linked disorders, females will show mild to moderate symptoms. This milder manifestation of an X-linked disorder in females may be related, in part, to the fact that most females have, in addition to a large number of cells expressing the abnormal gene, a large number of cells expressing the normal gene. Symptoms remain milder than those seen in affected males who carry no normal copy of the gene because they carry only a single X chromosome.

Some genes on the inactive X chromosome escape inactivation and remain active in females. These genes are believed to be responsible for many traits of normal females. The lack of these genes in females missing all or parts of a second X chromosome, as occurs in many cases of Turner syndrome, are thought to be associated with many of the clinical features of the syndrome.