One of the simplest and most important is through a positive feedback loop, where a master transcription regulator activates transcription of its own gene, in addition to that of other cell-typespecific genes. Each time a cell divides, the regulator is distributed to both daughter cells, where it continues to stimulate the positive feedback loop. The continued stimulation ensures that the regulator will continue to be produced in subsequent cell generations. Positive feedback is crucial for establishing the “self-sustaining” circuits of gene expression that allow a cell to commit to a particular fate—and then to transmit that decision to its progeny.

Although positive feedback loops are probably the most prevalent way of ensuring that daughter cells remember what kind of cells they are meant to be, there are other ways of reinforcing cell identity. One involves the methylation of DN In vertebrate cells, DNA methylation occurs on certain cytosine bases. This covalent modification generally turns off the affected genes by attracting proteins that bind to methylated cytosines and block gene transcription. DNA methylation patterns are passed on to progeny cells by the action of an enzyme that copies the methylation pattern on the parent DNA strand to the daughter DNA strand as it is synthesized.

Another mechanism for inheriting gene expression patterns involves the modification of histones. When a cell replicates its DNA, each daughter double helix receives half of its parent’s histone proteins, which contain the covalent modifications that were present on the parent chromosome. Enzymes responsible for these modifications may bind to the parental histones and confer the same modifications to the new histones nearby. It has been proposed that this cycle of modification helps reestablish. the pattern of chromatin structure found in the parent chromosome

Because all of these cell-memory mechanisms transmit patterns of gene expression from parent to daughter cell without altering the actual nucleotide sequence of the DNA, they are considered to be forms of epigenetic inheritance. These mechanisms, which work together, play an important part in maintaining patterns of gene expression, allowing transient signals from the environment to be remembered by our cells—a fact that has important implications for understanding how cells operate and how they malfunction in disease.