by PhilipJ on 15 April 2009
The development of a complete human being from a single cell is one of the great miracles of life. A human egg cell contains about 30,000 genes that encode proteins, and of these, about 3,000 of these genes encode transcription factors. Transcription factors determine when genes will be turned on and turned off, orchestrating the many processes involved in the development of an embryo and the many tasks performed by each cell after a child is born. Amazingly, there is only about 1 transcription factor for every 10 genes, posing a puzzle: how does this limited set of proteins control the many genes and processes that must be regulated?
One of the answers to this question may be discovered by looking at the binding sites for transcription factors in the genome. Typical genes in our cells have extensive regulatory regions before and after the genes, sometimes 100,000 base pairs away, and occasionally even inside the genes. These regions act in many different ways, as enhancers, silencers, insulators, and promotors of the gene. Each gene is controlled by a combination of many transcription factors, which together form a consensus as to whether the gene will be expressed or not at any given time.
Oct4 and its cofactor Sox2 are at the center of a collection of transcription factors that control the first decisions in the development of an embryo. Oct4 is present in embryonic stem cells, and its levels drop when the cell starts to divide and differentiate into different types of cells. It has been called the “gatekeeper” of development, since it is necessary for maintaining the stem cell state. The structure shown here, from PDB entry 1gt0, shows the DNA-binding portions of a similar protein, Oct1 (at the bottom in turquoise), and Sox2 (at the top in blue) bound to a short piece of DNA (in orange and pink).
Read the rest from David Goodsell at the RCSB PDB here.