Environmental stress triggers multilevel adaptations in animal development that depend in part on epigenetic mechanisms. In response to harsh environmental conditions and pheromone signals, Caenorhabditis elegans larvae become the highly stressresistant and long-lived dauer. Despite extensive studies of dauer formation pathways that integrate specific environmental cues and appear to depend on transcriptional reprogramming, the role of epigenetic regulation in dauer development has remained unclear. Here we report that BLMP-1, the BLIMP-1 ortholog, regulates dauer formation via epigenetic pathways; in the absence of TGF-b signaling (in daf-7 mutants), lack of blmp-1 caused lethality. Using this phenotype, we screened 283 epigenetic factors, and identified lin-40, a homolog of metastasis-associate protein 1 (MTA1) as an interactor of BLMP-1. The interaction between LIN-40 and BLMP-1 is conserved because mammalian homologs for both MTA1 and BLIMP-1 could also interact. From microarray studies, we identified several downstream target genes of blmp-1: npr-3, nhr-23, ptr-4, and sams-1. Among them S-adenosyl methionine synthase (SAMS-1), is the key enzyme for production of SAM used in histone methylation. Indeed, blmp-1 is necessary for controlling histone methylation level in daf-7 mutants, suggesting BLMP-1 regulates the expression of SAMS-1, which in turn may regulate histone methylation and dauer formation. Our results reveal a new interaction between BLMP-1/BLIMP-1 and LIN-40/MTA1, as well as potential epigenetic downstream pathways, whereby these proteins cooperate to regulate stress-specific developmental adaptations.KEYWORDS stress resistant development; BLMP-1; epigenetics; TGF-b; dauer D URING development, epigenetic changes in gene expression are passed on to the daughter cells to dictate cell fate without changing the DNA sequence itself (Hemberger et al. 2009). Epigenetic regulation is critical not only for normal development but also for tumor proliferation (Jones and Baylin 2007). The PRDM (PR domain-containing genes) family regulates many epigenetic events through interactions with histone modification and nucleosome remodeling factors (Hohenauer and Moore 2012;Pinheiro et al. 2012). Within this family, PRDM-1/BLIMP-1 regulates differentiation of various tissues and cell types including germ cells and B cells (Turner et al. 1994;Bikoff et al. 2009;John and Garrett-Sinha 2009). PRDM-1/BLIMP-1 is a transcriptional repressor, interacting with chromatin factors, such as the SET domain protein G9a (Yu et al. 2000), histone deacetylase HDAC1/2 (Gyory et al. 2004), and demethylase LSD1 (Su et al. 2009). Defects in the gene function are associated with certain type of lymphoma (Mandelbaum et al. 2010), demonstrating its critical role in B cell development. Termination of B cell differentiation is controlled by PRDM-1/BLIMP-1 ( Kallies et al. 2004) and an abnormal downregulation of PRDM-1/BLIMP-1 may prevent the terminal differentiation process in diffuse large B-cell lymphoma (Nie et al. 2010).Recentl...