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Topics in Depth

The Theme of Where Does it Start? in Gene to Protein

While some simple organisms like bacteria have highly organized genes on DNA, most organisms have their genes scattered within a random mess of DNA sequence. How does the cell know where to begin transcribing?

If you guessed that the cell begins by recognizing a specific DNA sequence, you are absolutely correct and totally on your way to becoming a transcription guru.

Proteins recognize a specific DNA "start" sequence, known as the promoter. This start sequence signals where transcription should begin. Eukaryotic polymerases are much more dependent that prokaryotes on additional accessory factors, called transcription factors, for everything from binding to the promoter to initialization of the polymerization reaction.

What does a promoter look like? This answer isn't exactly straightforward. Bacterial promoters are probably the easiest to define. They are located close to the start of transcription (called the +1 site). There are two relatively conserved DNA sequences, located in two patches upstream (toward the 3' end of the template). The first patch is located about 35 bases upstream of the +1 site, while a second often less conserved site is located about 10 base upstream. One of the subunits of the bacterial polymerase binds to the -35 sequence. These regions of the promoter are important not only for determining where transcription starts, but they also influence how often and how fast a gene is transcribed.

Bacteria are great and all, but what about you, right?

Eukaryotic promoters differ depending on which type of polymerase binds them. For RNA polymerase II, an important sequence located about 25 bases upstream is called the TATA box, because of the abundance of thymine and adenine bases in the sequence. In general though, the promoters of eukaryotic genes are much more loosely defined, and therefore more difficult to recognize. However eukaryotic promoters are alike in that they are bound by specific transcription factors that also influence how often the gene is transcribed. Upstream (and downstream) regulatory sequences—sequences that a protein binds to and regulates the transcription of the gene—are also important for regulating eukaryotic transcription. These sequences can be far away.

Starting to feel a little overwhelmed? Deal with it. Wouldn't you be a little insulted if you were as easy to understand as the tiny little microbes that live inside you?

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