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Recruitment of RNA polymerase II by the pioneer transcription factor PHA-4

Multifunctional pioneers Proteins surround cellular DNA to silence gene expression. Early in development, proteins such as pioneer transcription factors facilitate the opening of this silenced chromatin structure. Hsu et al. describe an additional role for the PHA-4 pioneer transcription factor in nematode worms. PHA-4 recruited RNA polymerase II to target promoters before transcriptional onset, and this activity preceded its chromatin-opening duty. The multifunctional role identified for PHA-4 may be shared by other pioneer factors. Science, this issue p. 1372 A transcription factor involved in cell-fate changes also facilitates chromatin opening. Pioneer transcription factors initiate cell-fate changes by binding to silent target genes. They are among the first factors to bind key regulatory sites and facilitate chromatin opening. Here, we identify an additional role for pioneer factors. In early Caenorhabditis elegans foregut development, the pioneer factor PHA-4/FoxA binds promoters and recruits RNA polymerase II (Pol II), often in a poised configuration in which Pol II accumulates near transcription start sites. At a later developmental stage, PHA-4 promotes chromatin opening. We found many more genes with poised RNA polymerase than had been observed previously in unstaged embryos, revealing that early embryos accumulate poised Pol II and that poising is dynamic. Our results suggest that Pol II recruitment, in addition to chromatin opening, is an important feature of PHA-4 pioneer factor activity.