Enhanceosome

keywords: transcription factor, gene expression, CBP, CREB-binding protein, transcriptional enhancers, enhanceosome

Take a moment to ponder the form of your body: the shape of your face, the color of your eyes, the length of your fingers, the perfect articulation of your bones and muscles, the way your hair grows curly or straight. Now let your imagination travel inward, and think of the complex shapes and functions of your different cells, and the teeming molecular world inside each one. Remarkably, this amazing structure and form and function is specified by information in the genome, which encodes a mere 20,000-25,000 protein-coding genes. One of the great puzzles being pieced together by scientists is the mechanism by which these genes, and the methods used to control their expression, specify all of these different aspects of life.

Combinatorial Control

In order to specify which gene will be expressed in a given situation, your cells use a diverse collection of DNA-binding proteins to control access to the DNA. Surprisingly, there are relatively few of these proteins: by some estimates, the human genome encodes about 2,600 of them. But then, the capabilities of this limited set are greatly expanded by using them in combination, by requiring two or more to bind simultaneously to activate a gene. In this way, each protein may be used in many ways and the spectrum of responses is far more varied.

Enhancing Transcription

The assembly of DNA and proteins pictured here is a transcriptional enhanceosome (PDB entries 1t2k, 2pi0, 2o6g and 2o61) that controls expression of interferon-beta, an important protein for fighting viral infection. When the cell is infected by viruses, several different DNA-binding proteins are produced, including ATF-2/c-Jun (in green at the top), interferon response factors (IRF, shown in turquoise at the center), and nuclear factor kB (NF-kB, shown in blue and magenta at the bottom). Individually, each one is not sufficient to activate the gene, and each one also plays other roles in the activation of other genes (for instance, Nf-kB is also important in immune responses, inflammation, apoptosis, and many other processes). But when they all bind together, they activate the gene and interferon is made.