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The expression of most genes is regulated by more than one transcription factor, with many genes being turned on or off using different combinations of proteins. This combinatorial gene control allows eukaryotes to precisely control transcription.
Combinatorial gene control can regulate whether a gene is transcribed, as well as its transcriptional efficiency. Consider three transcription factors, A, B, and C, which affect the transcription of a gene, X.
If A is absent, gene X will not be transcribed. If C is absent, gene X will not be transcribed. And if B is absent, transcriptional efficiency will decrease. Therefore, the combination of all three regulators is necessary for high levels of transcription of gene X.
A transcriptional regulator can participate in the regulation of multiple genes. A along with B and C cause the transcription of gene X, but A along with another transcription factor, D, can stimulate the transcription of a different gene, Y. This allows a few transcription factors to regulate a large number of genes.
Transcription factors are classified into different families and can function synergistically either with other proteins from the same family or with those from different families.
Transcription factors belonging to the POU family regulate genes with a variety of functions, ranging from housekeeping to cell differentiation; however, there are very few proteins in this family, with just fifteen in humans.
Their ability to perform their diverse functions depends on their coordination with other transcription factors from different families.
Combinatorial gene control is necessary for the in vitro reprogramming of differentiated cells. Expression of the transcription factors Oct-4, Sox-2, Klf-4, and c-Myc in somatic cells can trigger conversion to stem cells.
Reprogramming does not occur in the absence of any of the first 3 proteins, and the absence of c-Myc results in low-efficiency reprogramming. The combinatorial control of all four factors is necessary for the formation of induced pluripotent stem cells.
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of on…
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