Postrecruitment Regulation of RNA Pol II Directs Rapid Signaling Responses at the Promoters of Estrogen Target Genes

ABSTRACT: Under current models for signal-dependent transcription in eukaryotes, DNA-binding activator proteins regulate the recruitment of RNA polymerase II (Pol II) to a set of target promoters. Yet, recent studies, as well as our results herein, show that Pol II is widely distributed (i.e., "preloaded") at the promoters of many genes prior to specific signaling events. How Pol II recruitment and Pol II preloading fit within a unified model of gene regulation is unclear. In addition, the mechanisms through which cellular signals activate preloaded Pol II across mammalian genomes remain largely unknown. Here we show that the predominant genomic outcome of estrogen signaling is the post-recruitment regulation of Pol II activity through phosphorylation, rather than recruitment of Pol II. Furthermore, we show that negative elongation factor (NELF) binds to estrogen target promoters in conjunction with preloaded Pol II and represses gene expression until the appropriate signal is received. Finally, our studies reveal that the estrogen-dependent activation of preloaded Pol II facilitates rapid transcriptional and post-transcriptional responses which play important physiological roles in regulating estrogen signaling itself. Our results reveal a broad use of post-recruitment Pol II regulation by the estrogen signaling pathway, a mode of regulation that is likely to apply to a wide variety of signal-regulated pathways. ChIP-chip analysis for RNA Pol II, Ser5 phosphorylated RNA Pol II and NELF-A in MCF7 breast cancer cells.

ORGANISM(S): Homo sapiens

SUBMITTER: William Kraus 

PROVIDER: E-GEOD-13051 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress