Title: | BLIMP-1/BLMP-1 and Metastasis-Associated Protein Regulate Stress Resistant Development in Caenorhabditis elegans |
Author(s): | Hyun M; Kim J; Dumur C; Schroeder FC; You YJ; |
Address: | "Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298 Moonjung.Hyun@vcuhealth.org. Department of Biological Sciences, Inha University, Incheon, 402-751, South Korea. Department of Pathology, Virginia Commonwealth University, Richmond, Virginia 23298. Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853. Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298" |
DOI: | 10.1534/genetics.116.190793 |
ISSN/ISBN: | 1943-2631 (Electronic) 0016-6731 (Print) 0016-6731 (Linking) |
Abstract: | "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 stress-resistant 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-beta 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: | "5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/*genetics/metabolism Animals Caenorhabditis elegans/genetics Caenorhabditis elegans Proteins/*genetics/metabolism Carrier Proteins/*genetics *Epigenesis, Genetic Gene Expression Regulation, Develop;" |
Notes: | "MedlineHyun, Moonjung Kim, Jeongho Dumur, Catherine Schroeder, Frank C You, Young-Jai eng P40 OD010440/OD/NIH HHS/ R01 DK080074/DK/NIDDK NIH HHS/ R01 GM088290/GM/NIGMS NIH HHS/ 2016/06/24 Genetics. 2016 Aug; 203(4):1721-32. doi: 10.1534/genetics.116.190793. Epub 2016 Jun 22" |