Transcription by RNA polymerase II (Pol II) is dynamically regulated by assembly of the core enzyme with mediator proteins, transcription factors and other auxiliary factors. Several core subunits are involved in tissue-specific transcription, including RPB3, which directly contacts the myogenic transcription factor myogenin and the transcription factor ATF4. Expression of RBP3 is tightly regulated during muscle differentiation. Now Claudio Passananti and colleagues report that its subcellular localization is also regulated during this process (see p. 4253). The authors show that RPB3 accumulates in the cytoplasm of cycling myogenic cells but migrates to the nucleus upon induction of differentiation. They then use two-hybrid analysis, together with coimmunoprecipitation and colocalization experiments in myogenic cells, to identify HCR (a gene product implicated in susceptibility to psoriasis) as the cytoplasmic RPB3-interacting protein. Finally, the authors demonstrate that knocking down HCR by RNAi in cycling myogenic cells results in migration of RBP3 to the nucleus. They therefore conclude that HCR provides a cytoplasmic docking site for RPB3 and suggest that this interaction represents an additional level of tissue-specific transcriptional regulation.