Project description:modENCODE_submission_2943 This submission comes from a modENCODE project of Michael Snyder. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We are identifying the DNA binding sites for 300 transcription factors in C. elegans. Each transcription factor gene is tagged with the same GFP fusion protein, permitting validation of the gene's correct spatio-temporal expression pattern in transgenic animals. Chromatin immunoprecipitation on each strain is peformed using an anti-GFP antibody, and any bound DNA is deep-sequenced using Solexa GA2 technology. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: OP198(official name : OP198 genotype : unc-119(ed3); wgIs198(mml-1::TY1 EGFP FLAG C; unc-119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The MML-1::EGFP fusion protein is expressed in the correct mml-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the MML-1 transcription factor. made_by : R Waterston ); Developmental Stage: L3; Genotype: unc-119(ed3); wgIs198(mml-1::TY1 EGFP FLAG C; unc-119); Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage L3; Target gene mml-1; Strain OP198(official name : OP198 genotype : unc-119(ed3); wgIs198(mml-1::TY1 EGFP FLAG C; unc-119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The MML-1::EGFP fusion protein is expressed in the correct mml-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the MML-1 transcription factor. made_by : R Waterston ); temp (temperature) 20 degree celsius
Project description:MML-1 (Myc and Mondo-Like) encodes a Myc superfamily protein which, together with its partner MXL-2 (Max-like), regulates lifespan via distinct gene sets important for longevity. It is also required for normal migration of ray precursor cells in the male tail and for proper epidermal expression of extracellular matrix component genes. MML-1 binds to MXL-2, required for its protein stability. The MML-1/MXL-2 complex activate transcription mostly via E-box elements.
Project description:Accumulating evidence has demonstrated the presence of inter-tissue communication regulating systemic aging, but the underlying molecular network has not been fully explored. We and others previously showed that two basic helix-loop-helix transcription factors, MML-1 and HLH-30, are required for lifespan extension in several longevity paradigms, including germline-less Caenorhabditis elegans. However, it is unknown what tissues these factors target to promote longevity. Here, using tissue-specific knockdown experiments, we found that MML-1 and its heterodimer partners MXL-2 and HLH-30 act primarily in neurons to extend longevity in germline-less animals. Neuronal functions of MML-1/MXL-2 and HLH-30 are also essential to prevent aging in non-neuronal tissues, including muscle and the intestine. Interestingly, however, both the temporal requirement and the downstream function of MML-1 in neurons were distinct from those of HLH-30. MML-1 was active early, while HLH-30 functioned later in life to sustain longevity in germline-less animals. Moreover, neuronal RNA interference (RNAi)-based transcriptome analysis revealed that the glutamate transporter GLT-5 is a novel downstream target of MML-1 but not HLH-30. Furthermore, the MML-1–GTL-5 axis in neurons is critical to prevent an age-dependent collapse of proteostasis and increased oxidative stress through autophagy and peroxidase MLT-7, respectively, in long-lived animals. Collectively, our study revealed that systemic aging is regulated by a novel molecular network involving neuronal MML-1 function in both neural and peripheral tissues.