The number of DNA sequences and transcription factors that regulate transcription is much greater than originally anticipated. Most genes contain at least 15–20 discrete regulatory elements within 300 bp of the transcription start site. This densely packed promoter region often contains binding sites for ubiquitous transcription factors such as CAAT box/enhancer binding protein (C/EBP), cyclic AMP response element–binding (CREB) protein, selective promoter factor 1 (Sp-1), or activator protein 1 (AP-1). However, factors involved in cell-specific expression may also bind to these sequences. For example, basic helix-loop-helix (bHLH) proteins bind to E-boxes in the promoters of myogenic genes, and steroidogenic. | Chapter 062. Principles of Human Genetics Part 6 The number of DNA sequences and transcription factors that regulate transcription is much greater than originally anticipated. Most genes contain at least 15-20 discrete regulatory elements within 300 bp of the transcription start site. This densely packed promoter region often contains binding sites for ubiquitous transcription factors such as CAAT box enhancer binding protein C EBP cyclic AMP response element-binding CREB protein selective promoter factor 1 Sp-1 or activator protein 1 AP-1 . However factors involved in cell-specific expression may also bind to these sequences. For example basic helix-loop-helix bHLH proteins bind to E-boxes in the promoters of myogenic genes and steroidogenic factor 1 SF-1 binds to a specific recognition site in the regulatory region of multiple steroidogenic enzyme genes. Key regulatory elements may also reside at a large distance from the proximal promoter. The globin and the immunoglobulin genes for example contain locus control regions that are several kilobases away from the structural sequences of the gene. Specific groups of transcription factors that bind to these promoter and enhancer sequences provide a combinatorial code for regulating transcription. In this manner relatively ubiquitous factors interact with more restricted factors to allow each gene to be expressed and regulated in a unique manner that is dependent on developmental state cell type and numerous extracellular stimuli. As described below the transcription factors that bind to DNA actually represent only the first level of regulatory control. Other proteins coactivators and co-repressors interact with the DNA-binding transcription factors to generate large regulatory complexes. These complexes are subject to control by numerous cell-signaling pathways including phosphorylation acetylation sumoylation and ubiquitinylation. Ultimately the recruited transcription factors interact with and stabilize components
