| Citation | Rizki G, Iwata TN, Li J, Riedel CG, Picard CL, Jan M, Murphy CT, Lee SS. The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet, 2011. |
| PubMed ID | 21909281 |
| Short Description | The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. GEO Record: GSE30725 Platform: GPL13922 Download gene-centric, log2 transformed data: WBPaper00040184.ce.mr.csv |
| # of Conditions | 28 |
Full Description
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The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins. Experimental Details: WBPaper00040184:M2-S1(0.005):daf-16(RX5);hcf-1(pk924)(YA)_vs_hcf-1(pk924)(YA) WBPaper00040184:M2-S1(0.1):daf-16(RX5);hcf-1(pk924)(YA)_vs_hcf-1(pk924)(YA) WBPaper00040184:M2-S1(1):daf-16(RX5);hcf-1(pk924)(YA)_vs_hcf-1(pk924)(YA) WBPaper00040184:M2-S2(0.005):daf-16(RX5);hcf-1(pk924)(YA)_vs_hcf-1(pk924)(YA) WBPaper00040184:M2-S2(0.1):daf-16(RX5);hcf-1(pk924)(YA)_vs_hcf-1(pk924)(YA) WBPaper00040184:M2-S2(1):daf-16(RX5);hcf-1(pk924)(YA)_vs_hcf-1(pk924)(YA) WBPaper00040184:M2-S3(0.005):hcf-1(pk924)(YA)_vs_daf-16(RX5);hcf-1(pk924)(YA) WBPaper00040184:M2-S3(0.1):hcf-1(pk924)(YA)_vs_daf-16(RX5);hcf-1(pk924)(YA) WBPaper00040184:M2-S3(1):hcf-1(pk924)(YA)_vs_daf-16(RX5);hcf-1(pk924)(YA) WBPaper00040184:M2-S4(0.005):hcf-1(pk924)(YA)_vs_daf-16(RX5);hcf-1(pk924)(YA) WBPaper00040184:M2-S4(0.1):hcf-1(pk924)(YA)_vs_daf-16(RX5);hcf-1(pk924)(YA) WBPaper00040184:M2-S4(1):hcf-1(pk924)(YA)_vs_daf-16(RX5);hcf-1(pk924)(YA) WBPaper00040184:M3-S1(0.005):N2(YA)_vs_hcf-1(pk924)(YA) WBPaper00040184:M3-S1(0.1):N2(YA)_vs_hcf-1(pk924)(YA) WBPaper00040184:M3-S1(0.5):N2(YA)_vs_hcf-1(pk924)(YA) WBPaper00040184:M3-S1(1):N2(YA)_vs_hcf-1(pk924)(YA) WBPaper00040184:M3-S2(0.005):hcf-1(pk924)(YA)_vs_N2(YA) WBPaper00040184:M3-S2(0.1):hcf-1(pk924)(YA)_vs_N2(YA) WBPaper00040184:M3-S2(0.5):hcf-1(pk924)(YA)_vs_N2(YA) WBPaper00040184:M3-S2(1):hcf-1(pk924)(YA)_vs_N2(YA) WBPaper00040184:M3-S3(0.005):daf-16(RX5);hcf-1(pk924)(L4)_vs_hcf-1(pk924)(L4) WBPaper00040184:M3-S3(0.1):daf-16(RX5);hcf-1(pk924)(L4)_vs_hcf-1(pk924)(L4) WBPaper00040184:M3-S3(0.5):daf-16(RX5);hcf-1(pk924)(L4)_vs_hcf-1(pk924)(L4) WBPaper00040184:M3-S3(1):daf-16(RX5);hcf-1(pk924)(L4)_vs_hcf-1(pk924)(L4) WBPaper00040184:M3-S4(0.005):hcf-1(pk924)(L4)_vs_daf-16(RX5);hcf-1(pk924)(L4) WBPaper00040184:M3-S4(0.1):hcf-1(pk924)(L4)_vs_daf-16(RX5);hcf-1(pk924)(L4) WBPaper00040184:M3-S4(0.5):hcf-1(pk924)(L4)_vs_daf-16(RX5);hcf-1(pk924)(L4) WBPaper00040184:M3-S4(1):hcf-1(pk924)(L4)_vs_daf-16(RX5);hcf-1(pk924)(L4). |
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