Abstract
The rate of transcription initiation is the main level of quantitative control of gene expression, primarily responsible for the accumulation of mRNAs in the cell. Many, if not all, molecular actors involved in transcription initiation are known but the mechanisms underlying the frequency of initiations, remain elusive. To make the connection between transcription factors and the frequency of transcription initiation, intricated aspects of this complex activity are classified i) depending on whether or not the DNA-bound transcription factors directly activate the commitment to transcription and ii) on the destructive or non-destructive effect of transcription initiation on the stability of promoter complexes. Two possible sources of synergy allowing the combinatorial specificity of transcription factors action are compared, for binding to DNA and for recruiting transcription machineries. Tentative formulations are proposed to discriminate the different micro-reversible modes of DNA binding cooperativity modulating the specificity and dosage of transcription initiation.
Highlights
A wide variety of chromatin components are described, with different variants and modifications
Initiation irrevocably following DNA-binding (ID2) If transcription factor (TF) binding to DNA systematically leads to a series of events directing the departure of Pol Eukaryotic RNA-polymerase which transcribes protein-coding genes (II), the resulting transcription rate is a simplification of the ID1 equation when kS >> k1, k-1
Despite the number of reports on TFs, the very physical principles of transcription initiation remain largely obscure, and the wealth of descriptive observations has to be integrated in a coherent conceptual framework to facilitate their analysis and to plan rational future developments
Summary
A wide variety of chromatin components are described, with different variants and modifications. The innermost principles underlying the transcription initiation rate, which is the preponderant level of regulation of gene expression, are rarely addressed. Relatively few articles deal with the interesting concept of transcription reinitiation, of fundamental importance for setting the transcription rates. Studies are more focused on the time distribution than the regulation of the average frequency of transcriptional events, probably because of the general interest for biological randomness. A series of elementary principles of transcription initiation are revisited in the present study, more focused on general mechanisms than on particular actors, and starting from the reinterpretation of key data from the literature. Given the variety of reports on the regulation of transcription, this review cannot be fully comprehensive. Particular examples more thoroughly documented, are selected to illustrate generalizations, such as the Bicoid (BCD)/Hunchback (HB) system. A few simple examples from eubacteria will be given for comparison
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