Activation of the Ras-ERK MAP kinase signaling pathway leads to the phosphorylation and regulation of a series of transcription factors. This in turn leads to profound changes in cellular gene expression profiles and results in changes in cellular behavior. One important class of ERK target genes are the immediate-early genes whose expression is rapidly induced following activation of this pathway. Many of these events are coordinated through a transcription factor complex containing SRF and an ETS transcription factor from the TCF subfamily. ELK1 is the best studied of these TCFs and is directly phosphorylated by ERK. This in turn triggers a complex series of molecular events culminating in enhanced RNA pol II recruitment and elongation. The majority of these molecular processes have been elucidated on the FOS promoter but our recent studies have implicated ELK1 in the regulation of hundreds of genes, and a significant proportion of these targets appear to be controlled through the ELK1-SRF complex. Moreover, we have also conducted a genome-wide siRNA screen for additional regulators of ELK1 function, which has resulted in the identification of numerous regulators of the ERK-ELK1 signaling axis. One target from this screen, UBE3A, has been characterized and shown to be important in controlling ERK activation levels, and also the activation kinetics of downstream immediate-early genes. The role of this novel pathway regulator will be discussed in the context of our developing framework of the mechanisms by which immediate-early gene transcription is controlled. Our current model for immediate-early gene regulation explains how ERK-mediated phosphorylation of ELK1 triggers a complex series of downstream regulatory events, including transcription factor recruitment, histone modifications, and nucleosomal remodeling in target gene promoters.