Transcriptional Gene Regulation in Eukaryotes

Abstract Regulation of gene transcription is the primary means by which gene expression is controlled to produce different proteins in different cell types or in response to different stimuli. This process is controlled by transcription factors that belong to specific families which are defined on the basis of the different protein domains used to bind to deoxyribonucleic acid (DNA). Many transcription factors contain specific activation domains which allow them to activate transcription. In contrast, other transcription factors repress transcription either directly or indirectly by interfering with positively acting factors. Moreover, DNA‐binding transcription factors can also interact with one another and with non‐DNA‐binding coactivators and corepressors so allowing an individual transcription factor to differentialy regulate different genes. In turn, transcription factors are themselves regulated by controlling either their synthesis or by activating them from a pre‐existing inactive state by mechanisms such as ligand binding, phosphorylation or dissociation of an inhibitory protein. These mechanisms allow cellular differentiation events or specific signals to regulate gene expression by altering the synthesis and/or activity of individual transcription factors and thereby altering the expression of their target genes. Key Concepts: Regulation of the transcription of DNA into RNA is the key event controlling gene expression. Transcription is regulated by specific proteins called transcription factors. Many of these factors act by binding to specific DNA sequences in gene promoters or enhancers. Transcription factors bind to the DNA via specific DNA‐binding domains which differ between different transcription factor families. Following DNA binding, some factors activate transcription via specific activation domains. Other transcription factors can repress transcription either directly or indirectly by interfering with the action of positively acting factors. In order to regulate gene transcription, transcription factors are themselves regulated by controlling either their synthesis or their activity. The rate of transcription of a particular gene is therefore determined by the balance between the levels/activity of the activating and inhibitory transcription factors which act on it.