Gene expression can be controlled at different levels along the molecular pathway from DNA to protein, including the alteration of gene structure, transcription, mRNA processing, mRNA stability, translation, and posttranslational modification. Much of gene regulation takes place through the action of regulatory gene products that recognize and bind to regulatory elements.
Genes in bacterial cells are typically clustered into operons—
In negative control, a repressor protein binds to DNA and inhibits transcription. In positive control, an activator protein binds to DNA and stimulates transcription. In inducible operons, transcription is normally off and must be turned on; in repressible operons, transcription is normally on and must be turned off.
The lac operon of E. coli is a negative inducible operon. In the absence of lactose, a repressor binds to the operator and prevents the transcription of genes that encode β-galactosidase, permease, and transacetylase. When lactose is present, some of it is converted into allolactose, which binds to the repressor and makes it inactive, allowing the structural genes to be transcribed.
Positive control in the lac and other operons occurs through catabolite repression. When complexed with cAMP, the catabolite activator protein binds to a site in or near the promoter and stimulates the transcription of the structural genes. Levels of cAMP are inversely correlated with glucose, so low levels of glucose stimulate transcription and high levels inhibit transcription.
The trp operon of E. coli is a negative repressible operon that controls the biosynthesis of tryptophan.
Eukaryotic cells differ from bacteria in several ways that affect gene regulation, including, in eukaryotes, the absence of operons, the presence of chromatin, and the presence of a nuclear membrane.
In eukaryotic cells, chromatin structure represses gene expression. In transcription, chromatin structure may be altered by chromatin-
The initiation of eukaryotic transcription is controlled by general transcription factors that assemble into the basal transcription apparatus and by transcriptional regulator proteins that stimulate or repress normal levels of transcription by binding to regulatory promoters and enhancers.
Enhancers affect the transcription of distant genes. Regulatory proteins bind to enhancers and interact with the basal transcription apparatus by causing the intervening DNA to loop out. Insulators limit the action of enhancers by blocking their action in a position-
Coordinately controlled genes in eukaryotic cells respond to the same factors because they have common response elements that are stimulated by the same transcriptional activator.
Gene expression in eukaryotic cells can be influenced by RNA processing and by changes in mRNA stability. The 5′ cap, the poly(A) tail, the 5′ UTR, the coding region, and sequences in the 3′ UTR are important in controlling the stability of eukaryotic mRNAs.
RNA interference plays an important role in eukaryotic gene regulation. Small RNA molecules (siRNAs and miRNAs) combine with proteins and bind to sequences on mRNA or DNA. These complexes cleave RNA, inhibit translation, affect RNA degradation, and silence transcription.
Posttranslational modification of proteins may play a role in the regulation of gene expression.
Arabidopsis thaliana possesses a number of characteristics that make it an ideal model genetic organism.
Epigenetic effects—
Many epigenetic phenotypes result from changes to chromatin structure. Epigenetic effects occur through DNA methylation, histone modifications, and RNA molecules.
Paramutation is a heritable alteration of one allele by another allele, without any change in DNA sequence.
Early life experiences can produce epigenetic changes that have long-
The epigenome is the complete set of chromatin modifications possessed by an individual organism.