in the number of genes being transcribed at a specific time. In mammalian cells, the number of active rDNA genes varies between cell types and level of differentiation. In general, as a cell becomes more differentiated, it requires less growth and, therefore, will have a decrease in rRNA synthesis and a decrease in rDNA genes being transcribed. When rRNA synthesis is stimulated, SL1 (selectivity factor 1) will bind to the promoters of rDNA genes that were previously silent, and recruit a pre-initiation complex to which Pol I will bind and start transcription of rRNA. Changes in rRNA transcription can also occur via changes in the rate of transcription. While the exact mechanism through which Pol I increases its rate of transcription is as yet unknown, evidence has shown that rRNA synthesis can increase or decrease without changes in the number of actively transcribed rDNA. Transcription cycle In the process of transcription (by any polymerase), there are three main stages: Initiation: the construction of the RNA polymerase complex on the gene's promoter with the help of transcription factors Elongation: the actual transcription of the majority of the gene into a corresponding RNA sequence Termination: the cessation of RNA transcription and the disassembly of the RNA polymerase complex. Initiation Pol I requires no TATA box in the promoter, instead relying on an upstream control element (UCE) located between −200 and −107, and a core element located between −45 and +20. The dimeric eukaryotic upstream binding factor (UBF) binds the UCE and the core element. UBF recruits and binds a protein complex called SL1 in humans (or TIF-IB in mouse), composed of the TATA-binding protein (TBP) and three TBP-associated factors (TAFs). The UBF dimer contains several high-mobility-group boxes (HMG-boxes) that introduce loops into the upstream region, allowing the UCE and the core elements to come into contact. RRN3/TIF-IA is phosphorylated and binds Pol I. Pol I binds to the UBF/SL1 complex via RRN3/TIF-IA, and transcription starts. Note that this process is variable in different organisms. Elongation As Pol I escapes and clears the promoter, UBF and SL1 remain-promoter bound, ready to recruit another Pol I. Indeed, each active rDNA gene can be transcribed multiple times simultaneously, as opposed to Pol II-transcribed genes, which associate with only one complex at a time. While elongation proceeds unimpeded in vitro, it is unclear at this point whether this process happens in a cell, given the presence