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Regulation of Gene Expression in Eukaryotes:- Many Eukaryotic Promoters Are Positively Regulated

المؤلف:  David L. Nelson، Michael M. Cox

المصدر:  Lehninger Principles of Biochemistry

الجزء والصفحة:  p1103-1104

2026-08-02

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Regulation of Gene Expression in Eukaryotes:- Many Eukaryotic Promoters Are Positively Regulated

As already noted, eukaryotic RNA polymerases have little or no intrinsic affinity for their promoters; initiation of transcription is almost always dependent on the action of multiple activator proteins. One important reason for the apparent predominance of positive regulation seems obvious: the storage of DNA within chromatin effectively renders most promoters inaccessible, so genes are normally silent in the absence of other regulation. The structure of chromatin affects access to some promoters more than others, but repressors that bind to DNA so as to preclude access of RNA polymerase (negative regulation) would often be simply redundant. Other factors are at play in the use of positive regulation, and speculation generally centers around two: the large size of eukaryotic genomes and the greater efficiency of positive regulation. First, nonspecific DNA binding of regulatory proteins becomes a more important problem in the much larger genomes of higher eukaryotes. And the chance that a single specific binding sequence will occur randomly at an inappropriate site also increases with genome size. Specificity for transcriptional activation can be improved if each of several positive-regulatory proteins must bind specific DNA sequences and then form a complex in order to become active. The average number of regulatory sites for a gene in a multicellular organism is probably at least five. The requirement for binding of several positive-regulatory proteins to specific DNA sequences vastly reduces the probability of the random occurrence of a functional juxtaposition of all the necessary binding sites. In principle, a similar strategy could be used by multiple negative-regulatory elements, but this brings us to the second reason for the use of positive regulation: it is simply more efficient. If the 30,000 to 35,000 genes in the human genome were negatively regulated, each cell would have to synthesize, at all times, this same number of different repressors (or many times this number if multiple regulatory elements were used at each promoter) in concentrations sufficient to permit specific binding to each “un wanted” gene. In positive regulation, most of the genes are normally inactive (that is, RNA polymerases do not bind to the promoters) and the cell synthesizes only the activator proteins needed to promote transcription of the subset of genes required in the cell at that time. These arguments notwithstanding, there are examples of negative regulation in eukaryotes, from yeast to hu mans, as we shall see.