Genome-wide chromatin localization profiling of transcription factor MML-1
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ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE123393 | GEO | 2024/06/07
REPOSITORIES: GEO
Similar Datasets
Project description:Comprehensive transcriptome analysis of hlh-30, mml-1 and mxl-2 in N2 (wildtype) and glp-1 background.
2016-03-21 | E-MTAB-3686 | biostudies-arrayexpress
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.
2023-09-18 | GSE234429 | GEO
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.
2023-09-18 | GSE234430 | GEO
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
2013-07-11 | E-GEOD-48688 | biostudies-arrayexpress
Project description:Dietary restriction (DR), the process of decreasing overall food consumption over an extended period of time, has been shown to increase longevity across evolutionarily diverse species and delay the onset of age-associated diseases in humans. In Caenorhabditis elegans, the Myc-family transcription factors (TFs) MXL-2 (Mlx) and MML-1 (MondoA/ChREBP), which function as obligate heterodimers, and the forkhead box transcription factor A ortholog (PHA-4) are both necessary for the full physiological benefits of DR. However, the adaptive transcriptional response to DR and the role of MML-1::MXL-2 and PHA-4 remains elusive. We identified the transcriptional signature of C. elegans DR, using the eat-2 genetic model, and demonstrate broad changes in metabolic gene expression in eat-2 DR animals, which requires both mxl-2 and pha-4. While the requirement for these factors in DR gene expression overlaps, we found many of the DR genes exhibit an opposing change in relative gene expression in eat-2;mxl-2 animals compared to wild-type, which was not observed in eat-2 animals with pha-4 loss. We further show functional deficiencies of the mxl-2 loss in DR outside of lifespan, as eat-2;mxl-2 animals exhibit substantially smaller brood sizes and lay a proportion of dead eggs, indicating that MML-1::MXL-2 has a role in maintaining the balance between resource allocation to the soma and to reproduction under conditions of chronic food scarcity. While eat-2 animals do not show a significantly different metabolic rate compared to wild-type, we also find that loss of mxl-2 in DR does not affect the rate of oxygen consumption in young animals. The gene expression signature of eat-2 mutant animals is consistent with optimization of energy utilization and resource allocation, rather than induction of canonical gene expression changes associated with acute metabolic stress -such as induction of autophagy after TORC1 inhibition. Consistently, eat-2 animals are not substantially resistant to stress, providing further support to the idea that chronic DR may benefit healthspan and lifespan through efficient use of limited resources rather than broad upregulation of stress responses, and also indicates that MML-1::MXL-2 and PHA-4 may have different roles in promotion of benefits in response to different pro-longevity stimuli.
2023-12-13 | GSE240821 | GEO
Project description:Neuronal MML-1/MXL-2 regulates autophagic and peroxidase activity via glutamate transporter to prolong lifespan
| PRJNA981230 | ENA
Project description:Transcriptional control is mediated by interactions of transcription factors with their cognate DNA elements, as well as by epigenetic modifications to chromatin catalyzed by a variety of enzymes. Thus, understanding the crosstalk between transcription factors and epigenetic modifiers is of prime importance. The Dot1-like protein (DOT1L) is an evolutionary conserved methyltransferase with catalytic specificity towards histone 3 lysine 79 (H3K79). DOT1L is essential for mammalian development and has been studied mostly in the context of aggressive leukemias. Recent observations suggest that the role of DOT1L in malignant transformation can be generalized to contexts beyond leukemia. For instance, DOT1L has been implicated in breast cancer progression, and this has been attributed to its cooperation with c-Myc. However, the mechanistic details underlying this association are unknown. Previous work in our lab has shown that DOT-1.1, the C. elegans DOT1L homologue, is recruited to chromatin by ZFP-1 (similarly to DOT1L recruitment by AF10 in mammals), and this complex negatively modulates transcription. Interestingly, promoters of ZFP-1/DOT-1.1 target genes are enriched in E-boxes, the consensus binding motif for c-Myc. Prompted by the exciting hypothesis that DOT-1.1 and MML-1, the C. elegans c-Myc homologue, cooperate genome-wide, we profiled gene expression in wild-type worms and dot-1.1(gk105059), zfp-1(ok554), and mml-1(gk402844) loss-of-function mutants by microarray. We found significant overlaps between genes upregulated in the three mutants, and the same was observed for downregulated genes. A significant global increase of non-coding transcripts was observed in either mutant compared with wild-type. Therefore, ZFP-1/DOT-1.1 and MML-1 co-regulate both coding and non-coding genes and globally inhibit non-coding transcription. Further investigation is underway to uncover the mechanism of cooperation of ZFP-1/DOT-1.1 and MML-1. Profiling of gene expression in wild-type third larval stage (L3) larvae and zfp-1(ok554), dot-1.1(gk105059) and mml-1(gk402844) mutant worms.
2021-09-09 | GSE115677 | GEO
Project description:Neuronal HLH-30 regulates glp-1 longevity independent of neuronal MML-1/MXL-2
| PRJNA981229 | ENA
Project description:Genome-wide chromatin localization profiling of transcription factor MML-1
| PRJNA508616 | ENA
Project description:MML-1/Mondo complexes regulate HLH-30/TFEB via TOR inhibition to promote longevity in response to signals from the reproductive system
| PRJEB9736 | ENA