We present a molecular model of eukaryotic gene transcription. For the beta-globin locus, we hypothesise that a transcription machine composed of multiple RNA polymerase II (PolII) assembles using the locus control region as a foundation. Transcription and locus remodelling can be achieved by pulling DNA through this multi-PolII 'reading head'. Once a transcription complex is formed, it may engage an active gene in several rounds of transcription. Observed intergenic sense and antisense transcripts may be the result of PolII pulling the DNA through the reading head whilst searching for the promoter of a gene. Support for this hypothesis is provided using various data from the literature. In the model, DNA is packed in a 30-nm chromatin fibre, thus gene regulatory regions separated by kilobases are close in space. This, and the need to store transcription-induced supercoiling, may explain why functionally interacting regions are often separated by many kilobases.
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