Table 2.
A Summary of Key Genes from Each Cluster
| Cluster | Gene* | Gene (description) | Gene ontology (GO) group | GO P value† | Max fc/groups‡ | MIF ref.§ |
|---|---|---|---|---|---|---|
| A, Up-regulation by MIF, Ovx interaction | ||||||
| Tnnc | Troponin C, cardiac/slow skeletal | Muscle contraction | 0.00000728 | 7.0/A versus B | x | |
| Tpm3 | Tropomyosin 3 | Muscle contraction | 0.00000728 | 4.1/A versus B | x | |
| Cxcl5 | Chemokine (C-X-C motif) ligand 5 | Immune/defense response | 0.00472 | 5.0/A versus B | √ | |
| C1qb | Complement component 1q, β | Immune/defense response | 0.00472 | 4.9/A versus B | √ | |
| Il6 | Interleukin 6 | Immune/defense response | 0.00472 | 2.9/A versus B | √ | |
| Prg4 | Proteoglycan 4 | Extracellular | 0.000336 | 6.0/A versus B | x | |
| Cd163 | CD163 antigen | Extracellular | 0.000336 | 3.7/A versus B | x | |
| Fbn1 | Fibrillin 1 | Extracellular matrix | 0.000615 | 2.1/A versus B | x | |
| Ets1 | E26 avian leukemia oncogene 1 | Anti-apoptosis/Binding | 0.0256 | 3.1/A versus B | x | |
| B, Up-regulation by MIF, Ovx interaction | ||||||
| Timp1 | Tissue inhibitor of metalloproteinase 1 | Extracellular | 1.74E-09 | 4.1/A versus B | √ | |
| Pdgfra | Platelet derived growth factor receptor, a | Extracellular | 1.74E-09 | 3.7/A versus B | x | |
| Myh6 | Myosin, heavy polypeptide 6, cardiac a | Muscle development | 0.0000391 | 3.7/A versus B | x | |
| Lox | Lysyl oxidase | Oxidoreductase activity | 0.0149 | 3.7/A versus B | x | |
| Cd36 | CD36 antigen | Cell adhesion | 0.00911 | 3.5/A versus B | x | |
| Col4a1 | Procollagen, type IV, α1 | Extracellular matrix | 0.0000266 | 2.9/A versus B | √ | |
| Mfap5 | Microfibrillar associated protein 5 | Extracellular matrix | 0.0000266 | 2.4/A versus B | x | |
| Mmp2 | Matrix metalloproteinase 2 | Extracellular matrix | 0.0000266 | 2.0/A versus B | √ | |
| Vim | Vimentin | Intermediate filament | 0.00457 | 2.5/A versus B | x | |
| C, Up-regulation by MIF only | ||||||
| Mif | Macrophage migration inhibitory factor | Immune response | 0.0205 | 6.6/A versus C | n/a | |
| Col3a1 | Procollagen, type III, α1 | Collagen | 4.8E-15 | 5.9/A versus B | x | |
| Col1a1 | Procollagen, type I, α1 | Collagen | 4.8E-15 | 4.0/B versus C | x | |
| Col1a2 | Procollagen, type I, α2 | Collagen | 4.8E-15 | 3.6/A versus B | x | |
| Lum | Lumican | Extracellular matrix | 5.45E-17 | 3.6/B versus D | x | |
| Fbn1 | Fibrillin 1 | Extracellular matrix | 5.45E-17 | 3.4/B versus D | x | |
| Pcolce | Procollagen C-proteinase enhancer protein | Extracellular | 4.58E-20 | 3.1/A versus B | x | |
| Serpinh1 | Serine proteinase inhibitor clade H 1 | Extracelluar | 4.58E-20 | 2.6/B versus C | x | |
| Ndn | Necdin | Cell growth | 0.0042 | 2.6/A versus B | x | |
| D, Down-regulation by MIF, Ovx interaction | ||||||
| Krt1-15 | Keratin complex 1, acidic, gene 15 | Cytoskeleton | 0.000215 | 2.6/B versus D | x | |
| Wnt4 | Wingless-related MMTV integration site 4 | Cell communication | 0.0111 | 2.4/A versus B | x | |
| Fzd6 | Frizzled 6 | Cell communication | 0.0111 | 2.1/A versus B | x | |
| Notch1 | Notch gene homolog 1 | Cell communication | 0.0111 | 2.0/A versus B | x | |
| Cldn1 | Claudin 1 | Cell junction | 0.00133 | 2.3/A versus B | x | |
| Alox12e | Arachidonate lipoxygenase, epidermal | Oxidoreductase activity | 0.113 | 3.4/A versus B | x | |
| Defb6 | Defensin β6 | Extracellular | 0.121 | 2.7/A versus B | x | |
| E, Down-regulation by MIF, Ovx interaction | ||||||
| Jag1 | Jagged 1 | Morphogenesis | 0.00158 | 4.3/A versus B | x | |
| Dhcr24 | 24-Dehydrocholesterol reductase | Cell communication | 0.0176 | 2.6/A versus C | x | |
| Lhx2 | LIM homeobox protein 2 | Transcription | 0.0176 | 2.3/A versus B | x | |
| Sdc1 | Syndecan 1 | Membrane | 0.00963 | 2.2/A versus B | x | |
| St14 | Suppression of tumorigenicity 14 | Cell migration | 0.0857 | 2.0/A versus B | x | |
| Lad1 | Ladnin 1 | Extracellular matrix | 0.17 | 2.0/A versus B | x | |
| Alcam | Activated leukocyte cell adhesion molecule | Cell adhesion/membrane | 0.00963 | 1.8/A versus B | x | |
| Dsg2 | Desmoglein 2 | Intercellular junction | 0.0109 | 1.5/A versus B | x | |
| F, Down-regulation by MIF only | ||||||
| Thbs1 | Thrombospondin 1 | Extracellular | 0.177 | 3.8/C versus D | x | |
| Gbp1 | Guanylate nucleotide binding protein 1 | Immune response | 1.37E-11 | 3.2/C versus D | x | |
| Ifit1 | Interferon-induced with tetratricopeptide 1 | Immune response | 1.37E-11 | 2.5/B versus D | x | |
| Cxcl10 | Chemokine (C-X-C motif) ligand 10 | Immune response | 1.37E-11 | 2.5/B versus D | x | |
| Cdkn1a | p21 (CDKN1A)-activated kinase 1 | Immune response | 1.37E-11 | 1.7/A versus B | √ | |
| Mmp13 | Matrix metalloproteinase 13 | Extracellular matrix | 0.177 | 2.3/C versus D | √ | |
| Nfkbia | NF-k light chain enhancer in B-cell inhibitor, a | Cell proliferation | 0.00169 | 2.1/A versus B | √ | |
| G, Up-regulation by estrogen | ||||||
| Cyp2g1 | Cytochrome P450, family2, subfamily g,1 | Oxidoreductase activity | 0.00549 | 4.4/B versus D | x | |
| Cyp17a1 | Cytochrome P450, family17, subfamily a,1 | Oxidoreductase activity | 0.00549 | 1.8/B versus D | x | |
| Akr1c18 | Aldo-keto reductase family1, member C18 | Oxidoreductase activity | 0.00549 | 1.6/B versus D | x | |
| Fkbp5 | FK506 binding protein 5 | Chaperone activity/metabolism | 0.136 | 2.0/A versus D | x | |
| H, Down-regulation by estrogen | ||||||
| Cald1 | Caldesmon 1 | Actin binding | 0.285 | 2.5/B versus D | x | |
| Ramp2 | Receptor (calcitonin) activity modifying 2 | Growth/transport | 0.0189 | 2.8/A versus C | x | |
| Snx6 | Sorting nexin 6 | Growth/transport | 0.0189 | 1.8/A versus C | x | |
| Inhbb | Inhibin β-B | Growth/transport | 0.0189 | 1.6/B versus D | √ |
*
Genes in bold text have been validated by real-time PCR.
†
EASE-derived (see Materials and Methods) P value for overrepresentation of gene ontology (GO) group (bold indicates significance).
‡
Maximum fold change (fc) between any two experimental groups. In each case, experimental groups compared are defined: A, OVX, KO; B, OVX, WT; C, WT; and D, KO.
§
Known reference to MIF interaction; √, cited references to MIF regulation; x, novel MIF gene target.