a cytosine (one of the four base pairs that make up DNA). This leads to gene silencing because methylated DNA hinders the binding of transcription factors. A second major regulatory mechanism is related to the configuration of DNA. DNA is wrapped around clusters of histone proteins to form nucleosomes. Together the nucleosomes of DNA and histone are organized into chromatin. When the chromatin is tightly condensed, it is difficult for transcription factors to reach the DNA, and the gene is silenced. In contrast, when the chromatin is opened, the gene can be activated and expressed. Accordingly, modifications to the histone proteins that form the core of the nucleosome can affect the initiation of transcription by affecting how readily transcription factors can access the DNA and bind to their appropriate sequence.
