Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.

The promoters and enhancers and their accessory proteins allow tight regulation of transcription. The TATA box is the most widely studied among the different core promoter sequences, though it is only present in 10-15% of mammalian genes. The TATA box provides a platform for assembling the various transcription factors (TF), including TFIID, which contains the TATA-binding protein subunit. This assembly of transcription factors with the RNAP forms the pre-initiation complex (PIC). The PIC alone has a low transcription rate that other proteins called activators and repressors can enhance or decrease.

Once the RNAP has begun elongation, the transcription factors are released from the DNA to initiate another round of transcription with a new RNA polymerase molecule. The RNAP binds strongly to the DNA template and synthesizes the RNA transcript for long distances without dissociating from DNA.