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Expression cluster » WBPaper00040184:hcf-1nc_sir-2.1down_daf-2nc
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WBPaper00040184:hcf-1nc_sir-2.1down_daf-2nc
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)
Algorithm:
To identify the genes that show consistent and significant expression changes across the independent biological replicates of hcf-1(-) or sir-2.1(O/E), authors used Significance Analysis of Microarrays (SAM) with a stringent criteria of expected false discovery rate (FDR) set at 0%.Associations
| Life Stages | Definition |
|---|---|
| 1-day post-L4 adult hermaphrodite Ce | At 20 Centigrade: 24-48 hours after L4-adult molt. 4-5 days after first cleavage. |
| L4 larva Ce | The fourth stage larva. At 25 Centigrade, it ranges 40-49.5 hours after fertilization, 26-35.5 hours after hatch. |
References
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1
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.
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