A comprehensive analysis of the interactions between 106 transcription factors and regulatory sequences in the baker's yeast Saccharomyces cerevisiae revealed the presence of a number of common regulatory motifs302. These include:
•Autoregulatory loops: A transcription factor binds to sequences that regulate its own transcription. Such interactions can be positive (amplifying) or negative (squelching).
•Feed forward interactions: A transcription factor regulates the expression of a second transcription factor; the two transcription factors then cooperate to regulate the expression of a third gene.
•Regulatory chains: A transcription factor binds to the regulatory sequences in another gene and induces expression of a second transcription factor, which in turn binds to regulatory sequences in a third gene, etc. The chain ends with the production of some non-transcription factor products.
•Single and multiple input modules: A transcription factor binds to sequences in a number of genes, regulating their coordinated expression (σ factors works this way). In most cases, sets of target genes are regulated by sets of transcription factors that bind in concert.
In each case the activity of a protein involved in an interaction network can, like the lac repressor, be regulated through interactions with other proteins, allosteric factors, and post-translational modifications. It is through such interactions that signals from inside and outside the cell can control patterns of gene expression leading to maintenance of the homeostatic state or various adaptations.
Questions to answer & to ponder:
•Make a model for how a transcription factor determines which DNA strand will be transcribed.
•Make a model for how one could increase the specificity of the regulation of a specific gene.
•Describe the possible effects of mutations that alter the DNA-binding specificity of a transcription factor or a DNA sequence normally recognized by that transcription factor.
•Consider a particular gene, what factors are likely to influence the length of its regulatory region?
•What factors might drive the evolution of overlapping genes?
•How could you tell which X chromosome was inactivated in a particular cell of a female person?
•How would you design a regulatory network to produce a steady level of product?
•How can the activity of transcription factor proteins be regulated?
•How would regulating the intracellular localization of a transcription factor alter gene expression?
•What kinds of mutation would permanently inactivate a gene?
•Which type of regulatory interaction does the lac operon represent?
302 Transcriptional regulatory networks in Saccharomyces cerevisiae: http://www.ncbi.nlm.nih.gov/pubmed/12399584