Gene Regulation

Cell Memory

Cell memory is the process by which all progeny of a parent cell retain the specialization of that cell; DNA methylation is a marker for epigenetic inheritance.

Differentiated cells rarely revert to stem cells. However, they can divide to give rise to more cells of the same type. In order to ensure all daughter (new) cells retain the specialization of the original cells, they employ cell memory, the pattern of gene expression in daughter cells that gives them the same differentiation as the parent cell. The greatest mechanism that creates cell memory is the positive feedback loop—a mechanism that amplifies a physiological signal by increasing the body's response to a stimulus. In a positive feedback loop, a small variation from the baseline state triggers a signal to increase the variation. During cell memory, a positive feedback loop occurs when the transcription factors required to activate transcription of the proteins the cell must produce are transcribed on the gene they activate.

For example, consider that a cell must produce protein A in order to carry out its specialized function. To activate transcription of gene A, which produces protein A, transcription factor A is required. Gene A produces both a protein and genetic transcription factors. Thus, every time protein A is transcribed, transcription factor A is also transcribed along with it. Thus, even when the initial signal is gone, the cell retains the signal required to continue transcribing the necessary gene.

Positive Feedback Loop

A positive feedback loop allows daughter cells to retain the differentiation of their parent cell, a process called cell memory.
Positive feedback loops are the greatest driver of cell memory, but they are not the only one. Another mechanism used to keep cells in their pattern of differentiation is DNA methylation, the addition of methyl groups to cytosine nucleotides in the DNA strand, which condenses the DNA into heterochromatin and inhibits transcription. Methyl groups are molecules consisting of carbon atoms covalently bonded to three hydrogen atoms (CH3). Heterochromatin is tightly packed DNA and proteins. It is different from the more loosely packed euchromatin, which allows space for RNA polymerase to bind and initiate transcription. When a cell that has undergone DNA methylation divides, the methylated DNA is copied with the methylation as well so that all progeny (newly produced) cells have similarly methylated DNA, and transcription is inhibited in them all. DNA methylation is a marker for epigenetic inheritance, which is the transmission of information from parent cell to daughter cell without mutations in the genome. DNA methylation leads to the tighter compaction of DNA on a histone, the protein around which the DNA strand winds. Cells use a chemical reaction called acetylation, which causes histones to become more negatively charged. Because of this chemical change, not only is a histone stimulated to dissociate from DNA, but the process of transcription is also encouraged to occur.

DNA Methylation

DNA methylation, the addition of a methyl group to the cytosines in a DNA molecule, causes the chromatin to condense, reducing or blocking transcription because RNA polymerase cannot bind.
Cells also modify histones. Because each daughter cell receives one strand of DNA from its parent cell, the modified histones are received as well. The enzymes that cause the modification of the histones in the first place are drawn to the modified histones and then in turn modify the histones on the new strand as well. Thus all progeny cells will continue to have the histone modification.