9.1 Regulatory protein-DNA interactions
One of the most fascinating biological phenomena is the fact that a myriad of different cell types, in a multicellular organism, are encoded by one single genome. How exactly this is achieved is still a major unanswered question in biology. Cell types differ based on a multitude of features: their size, shape, mobility, surface receptors, metabolic content. However, the main predominant feature, which influences all of the above, is which genes are expressed in each cell type. Therefore, if we can understand what controls which genes will be expressed, and where they will be expressed, we can start forming a picture of how a single genomic template, can give rise to a complex organism.
As explained in Chapter 1, gene expression is controlled by a special class of genes called transcription factors - genes which control other genes. Transcription factor genes encode proteins which can bind to the DNA, and control whether a certain part of DNA will be transcribed (expressed), or stay silent (repressed). They program the expression patterns in each cell. Transcription factors contain DNA binding domains, which are specifically folded protein sequences which recognize specific DNA motifs (a short nucleotide sequence). Such sequence binding imparts transcription factors with specificity, transcription factors do not bind everywhere on the DNA, rather they are localized to short stretches which contain the corresponding DNA motif.
DNA in the nucleus is wrapped around a protein complex called the histone complex. Histones form a chain of beads along the DNA. By changing their position, histones can make certain parts of the DNA more or less accessible to transcription factors. Histone complexes can be chemically modified with different post-translational modifications (see Chapter 1). Such modifications change histone mobility, and their interactions with different proteins, thereby creating an additional regulatory layer on top of the DNA sequence.
In order to understand the target genes of a certain transcription factor, and how they control the gene expression, we need to know where on the DNA the transcription factor is located.