Supplementary Table 1. Genes with up-methylated promoters, their encoded proteins and annotated functions in the liver of vaccination-protected Balb/c mice infected with P. chabaudi on day 8 p.i. vs Vd0.
Gene symbol, name / Vd8-Vd0methylation
grade / NCBI
Gene ID / Encoded proteins and functions
Ank, progressive ankylosis / 0.7 / 11732 / “ANK is a multipass transmembrane protein that is expressed in joints and other tissues and controls pyrophosphate levels in cultured cells.”
Pou4f3, POU domain, class 4, transcription factor 3 / 1.2 / 18998 / “POU4F3 is a member of the POU-domain family of transcription factors. This protein is found in the retina and may play a role in determining or maintaining the identities of a small subset of visual system neurons.”
Cryz, crystallin, zeta / 0.8 / 12972 / “CRYZ is a taxon-specific crystallin protein which has NADPH-dependent quinone reductase activity distinct from other known quinone reductases.”
Taf9b, TATA-box binding protein associated factor 9B / 0.9 / 407786 / “TAF9B. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation.”
Dhx8, DEAH (Asp-Glu-Ala-His) box polypeptide 8 / 0.57 / 217207 / “DHX8 is a member of the DEAH box polypeptide family. It contains the DEAH (Asp-Glu-Ala-His) motif which is characteristic of all DEAH box proteins, and is thought to function as an ATP-dependent RNA helicase that regulates the release of spliced mRNAs from spliceosomes prior to their export from the nucleus. Among its related pathways are Signaling by GPCR and Interleukin receptor SHC signaling.”
Bmpr2, defensin beta 43 / 0.7 / 654458 / “BMPR2. Defensins are cysteine-rich cationic polypeptides that are important in the immunologic response to invading microorganisms.”
Tab3, TGF-beta activated kinase 1/MAP3K7 binding protein 3 / 0.83 / 66724 / “TAB3 functions in the NF-kappaB signal transduction pathway. The encoded protein, and the similar and functionally redundant protein MAP3K7IP2/TAB2, forms a ternary complex with the protein kinase MAP3K7/TAK1 and either TRAF2 or TRAF6 in response to stimulation with the pro-inflammatory cytokines TNF or IL-1. Subsequent MAP3K7/TAK1 kinase activity triggers a signaling cascade leading to activation of the NF-kappaB transcription factor.”
Corin, corin / 0.87 / 53419 / “CORINis a member of the type II transmembrane serine protease class of the trypsin superfamily. Members of this family are composed of multiple structurally distinct domains. This protein converts pro-atrial natriuretic peptide to biologically active atrial natriuretic peptide, a cardiac hormone that regulates blood volume and pressure.”
Psmc6, proteasome (prosome, macropain) 26S subunit, ATPase, 6 / 0.83 / 67089 / “PSMC6.The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. This protein is an ATPase subunit, a member of the triple-A family of ATPases which have a chaperone-like activity.”
Zic3, zinc finger protein of the cerebellum 3 / 0.97 / 22773 / “ZIC3is a member of the ZIC family of C2H2-type zinc finger proteins. This nuclear protein probably functions as a transcription factor in early stages of left-right body axis formation.”
Zfp384, zinc finger protein 384 / 0.8 / 269800 / “ZFP384 is a C2H2-type zinc finger protein, which may function as a transcription factor. This protein appears to bind and regulate the promoters of the extracellular matrix genes MMP1, MMP3, MMP7 and COL1A1. Studies in mouse suggest that nuclear matrix transcription factors (NP/NMP4) may be part of a general mechanical pathway that couples cell construction and function during extracellular matrix remodeling.”
Gyk, glycerol kinase / 0.77 / 14933 / “GYK belongs to the FGGY kinase family. It is a key enzyme in the regulation of glycerol uptake and metabolism. It catalyzes the phosphorylation of glycerol by ATP, yielding ADP and glycerol-3-phosphate.”
Ran,member RAS oncogene family / 0.93 / 19384 / “RAN (ras-related nuclear protein) is a small GTP binding protein belonging to the RAS superfamily that is essential for the translocation of RNA and proteins through the nuclear pore complex. It is also involved in control of DNA synthesis and cell cycle progression. Nuclear localization of RAN requires the presence of regulator of chromosome condensation 1 (RCC1). Mutations in RAN disrupt DNA synthesis. RAN regulates formation and organization of the microtubule network independently of its role in the nucleus-cytosol exchange of macromolecules. RCC1 generates a high local concentration of RAN-GTP around chromatin which, in turn, induces the local nucleation of microtubules. RAN is an androgen receptor (AR) coactivator that binds differentially with different lengths of polyglutamine within the androgen receptor.”
Lhx6, LIM homeobox protein 6 / 1 / 16874 / “LHX6 is a member of a large protein family that contains the LIM domain, a unique cysteine-rich zinc-binding domain.”
Trpc4ap, transient receptor potential cation channel, subfamily C, member 4 associated protein / 0.93 / 56407 / “TRPC4AP.Among its related pathways are transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Ion channel transport. Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control. The DCX(TRUSS) complex specifically mediates the polyubiquitination and subsequent degradation of MYC. Also participates in the activation of NFKB1 in response to ligation of TNFRSF1A, possibly by linking TNFRSF1A to the IKK signalosome. Involved in JNK activation via its interaction with TRAF2. Also involved in elevation of endoplasmic reticulum Ca(2+) storage reduction in response to CHRM1.”
Pnpla6, patatin-like phospholipase domain containing 6 / 1 / 50767 / “PNPLA6 is a phospholipase that deacetylates intracellular phosphatidylcholine to produce glycerophosphocholine. It is anchored to the cytoplasmic face of the endoplasmic reticulum in both neurons and non-neuronal cells.”
Kdm2b, lysine (K)-specific demethylase 2B / 0.67 / 30841 / “KDM2Bis a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. Histone demethylase that demethylates Lys-4 and Lys-36 of histone H3, thereby playing a central role in histone code. Preferentially demethylates trimethylated H3 Lys-4 and dimethylated H3 Lys-36 residue while it has weak or no activity for mono- and tri-methylated H3 Lys-36. Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation. May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.”
Stam2, signal transducing adaptor molecule (SH3 domain and ITAM motif) 2 / 0.93 / 56324 / “STAM2is closely related to STAM, an adaptor protein involved in the downstream signaling of cytokine receptors, both of which contain a SH3 domain and the immunoreceptor tyrosine-based activation motif (ITAM). Similar to STAM, this protein acts downstream of JAK kinases, and is phosphorylated in response to cytokine stimulation. This protein and STAM thus are thought to exhibit compensatory effects on the signaling pathway downstream of JAK kinases upon cytokine stimulation. STAM2 (Signal Transducing Adaptor Molecule (SH3 Domain And ITAM Motif) 2) is a Protein Coding gene. Among its related pathways are Signaling by GPCR and Interleukin receptor SHC signaling.”
Mars2, methionine-tRNA synthetase 2 / 0.83 / 212679 / “MARS2produces a mitochondrial methionyl-tRNA synthetase protein that is encoded by the nuclear genome and imported to the mitochondrion.”
Trmt12, tRNA methyltranferase 12 / 1.3 / 68260 / “TRMT12 is a S-adenosyl-L-methionine-dependent transferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. Catalyzes the transfer of the alpha-amino-alpha-carboxypropyl (acp) group from S-adenosyl-L-methionine to the C-7 position of 4-demethylwyosine (imG-14) to produce wybutosine-86.”
Mboat2, membrane bound O-acyltransferase domain containing 2 / 1.1 / 67216 / “MBOAT2 is an Acyltransferase which mediates the conversion of lysophosphatidylethanolamine (1-acyl-sn-glycero-3-phosphoethanolamine or LPE) into phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine or PE) (LPEAT activity). Catalyzes also the acylation of lysophosphatidic acid (LPA) into phosphatidic acid (PA) (LPAAT activity). Has also a very weak lysophosphatidylcholine acyltransferase (LPCAT activity). Prefers oleoyl-CoA as the acyl donor. Lysophospholipid acyltransferases (LPLATs) catalyze the reacylation step of the phospholipid remodeling pathway also known as the Lands cycle.”
Denr, density-regulated protein / 0.77 / 68184 / “DENR contains an SUI1 domain. In budding yeast, SUI1 is a translation initiation factor that along with eIF-2 and the initiator tRNA-Met, directs the ribosome to the proper translation start site. Proteins similar to SUI have been found in mammals, insects, and plants. Involved in translation initiation; promotes recruitmnet of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits.”
Mia3, melanoma inhibitory activity 3 / 0.67 / 338366 / “MIA3 is required for collagen VII (COL7A1) secretion by loading COL7A1 into transport carriers.”
Bambi, BMP and activin membrane-bound inhibitor / 0.7 / 68010 / “BAMBI is a transmembrane glycoprotein related to the type I receptors of the transforming growth factor-beta (TGF-beta) family, whose members play important roles in signal transduction in many developmental and pathological processes. This protein however is a pseudoreceptor, lacking an intracellular serine/threonine kinase domain required for signaling. Similar proteins in frog, mouse and zebrafish function as negative regulators of TGF-beta, which has led to the suggestion that the encoded protein may function to limit the signaling range of the TGF-beta family during early embryogenesis.”
Ift74, intraflagellar transport 74 / 0.93 / 67694 / “IFT74 is a component of the intraflagellar transport (IFT) complex B: together with IFT81, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium. Binds beta-tubulin via its basic region. Required for ciliogenesis.”
Ubtf, upstream binding transcription factor, RNA polymerase I / 0.87 / 21429 / “UBTF is a member of the HMG-box DNA-binding protein family. The encoded protein plays a critical role in ribosomal RNA transcription as a key component of the pre-initiation complex, mediating the recruitment of RNA polymerase I to rDNA promoter regions.”
Synj2, synaptojanin 2 / 0.7 / 20975 / “SYNJ2is a member of the inositol-polyphosphate 5-phosphatase family. This protein interacts with the ras-related C3 botulinum toxin substrate 1, which causes translocation of the encoded protein to the plasma membrane where it inhibits clathrin-mediated endocytosis.”
Alg10b, asparagine-linked glycosylation 10B (alpha-1,2-glucosyltransferase) / 0.83 / 380959 / “ALG10Bis a putative alpha-1,2-glucosyltransferase, which adds the third glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Glc(2)Man(9)GlcNAc(2)-PP-Dol.”
Ctnnbl1, catenin beta like 1 / 0.67 / 66642 / “CTNNBL1is a component of the pre-mRNA-processing factor 19-cell division cycle 5-like (PRP19-CDC5L) protein complex, which activates pre-mRNA splicing and is an integral part of the spliceosome. This protein is also a nuclear localization sequence binding protein, and binds to activation-induced deaminase and is important for antibody diversification. Participates in AID/AICDA-mediated Ig class switching recombination (CSR).”
Scamp1, secretory carrier membrane protein 1 / 0.77 / 107767 / “SCAMP1belongs to the SCAMP family of proteins, which are secretory carrier membrane proteins. They function as carriers to the cell surface in post-golgi recycling pathways. Different family members are highly related products of distinct genes, and are usually expressed together. Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface.”
Dst, dystonin / 0.87 / 13518 / “DST is a member of the plakin protein family of adhesion junction plaque proteins. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells or keratin-containing intermediate filaments to hemidesmosomes in epithelial cells.
Khk, ketohexokinase / 0.87 / 16548 / “KHK catalyzes conversion of fructose to fructose-1-phosphate. The product of this gene is the first enzyme with a specialized pathway that catabolizes dietary fructose. Alternatively spliced transcript variants encoding different isoforms have been identified. Catalyzes the phosphorylation of the ketose sugar fructose to fructose-1-phosphate.”
Ncoa5, nuclear receptor coactivator 5 / 0.77 / 228869 / “NCOA5 is a coregulator for the alpha and beta estrogen receptors and the orphan nuclear receptor NR1D2. The protein localizes to the nucleus, and is thought to have both coactivator and corepressor functions. Its interaction with nuclear receptors is independent of the AF2 domain on the receptors, which is known to regulate interaction with other coreceptors. Nuclear receptor coregulator that can have both coactivator and corepressor functions. Interacts with nuclear receptors for steroids (ESR1 and ESR2) independently of the steroid binding domain (AF-2) of the ESR receptors, and with the orphan nuclear receptor NR1D2. Involved in the coactivation of nuclear steroid receptors (ER) as well as the corepression of MYC in response to 17-beta-estradiol (E2).”
Tsfm, Ts translation elongation factor, mitochondrial / 0.67 / 66399 / “TSFM is a mitochondrial translation elongation factor. The encoded protein is an enzyme that catalyzes the exchange of guanine nucleotides on the translation elongation factor Tu during the elongation step of mitchondrial protein translation. Mutations in this gene are associated with combined oxidative phosphorylation deficiency-3 syndrome. Associates with the EF-Tu.GDP complex and induces the exchange of GDP to GTP. It remains bound to the aminoacyl-tRNA.EF-Tu.GTP complex up to the GTP hydrolysis stage on the ribosome.”
Trp53rk, transformation related protein 53 regulating kinase B / 0.83 / 76367 / “TRP53RKis a component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. Atypical protein kinase that phosphorylates Ser-15 of p53/TP53 protein and may therefore participate in its activation.”
Pfkl, phosphofructokinase, liver, B-type / 0.67 / 18641 / “PFKL is the liver (L) subunit of an enzyme that catalyzes the conversion of D-fructose 6-phosphate to D-fructose 1,6-bisphosphate, which is a key step in glucose metabolism (glycolysis). This enzyme is a tetramer that may be composed of different subunits encoded by distinct genes in different tissues. Alternative splicing results in multiple transcript variants. Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.”
Nup107, nucleoporin 107 / 0.8 / 103468 / “NUP107 is a member of the nucleoporin family. The protein is localized to the nuclear rim and is an essential component of the nuclear pore complex (NPC). All molecules entering or leaving the nucleus either diffuse through or are actively transported by the NPC. Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. Required for the assembly of peripheral proteins into the NPC.”
Rtn2, reticulon 2 (Z-band associated protein) / 1.17 / 20167 / “RTN2belongs to the family of reticulon encoding genes. Reticulons are necessary for proper generation of tubular endoplasmic reticulum and likely play a role in intracellular vesicular transport.”
Trim39, tripartite motif-containing 39 / 0.73 / 79263 / “TRIM39is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The function of this protein has not been identified. This gene lies within the major histocompatibility complex class I region on chromosome 6.”
Wnt2b, wingless-type MMTV integration site family, member 2B / 0.93 / 22414 / “WNT2Bis a member of the wingless-type MMTV integration site (WNT) family of highly conserved, secreted signaling factors. WNT family members function in a variety of developmental processes including regulation of cell growth and differentiation and are characterized by a WNT-core domain. Ligand for members of the frizzled family of seven transmembrane receptors.”
Pde4dip, phosphodiesterase 4D interacting protein (myomegalin) / 0.9 / 83679 / “PDE4DIP serves to anchor phosphodiesterase 4D to the Golgi/centrosome region of the cell. Defects in this gene may be a cause of myeloproliferative disorder (MBD) associated with eosinophilia.”
Grinl1a, polymerase (RNA) II (DNA directed) polypeptide M (Polr2m) / 0.8 / 28015 / “GRINL1A is a subunit of a specific form of RNA polymerase II termed Pol II(G). Isoform 1 appears to be a stable component of the Pol II(G) complex form of RNA polymerase II (Pol II). Pol II synthesizes mRNA precursors and many functional non-coding RNAs and is the central component of the basal RNA polymerase II transcription machinery. Isoform 1 acts in vitro as a negative regulator of transcriptional activation; this repression is relieved by the Mediator complex, which restores Pol II(G) activator-dependent transcription to a level equivalent to that of Pol II.”
Fem1a, feminization 1 homolog a / 0.93 / 14154 / “FEM1Ais probably a component of an E3 ubiquitin-protein ligase complex, in which it may act as a substrate recognition subunit (By similarity). May participate in antiinflammatory signaling via its interaction with PTGER4.”
1500002O20Rik, smg-9 homolog, nonsense mediated mRNA decay factor (C. elegans) (Smg9) / 0.9 / 71997 / “SMG-9 is involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited by release factors to stalled ribosomes together with SMG1 and SMG8 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required for the efficient association between SMG1 and SMG8.”
Car2, carbonic anhydrase 2 / 0.77 / 12349 / “CAR2is one of several isozymes of carbonic anhydrase, which catalyzes reversible hydration of carbon dioxide. Defects in this enzyme are associated with osteopetrosis and renal tubular acidosis. Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6. ”
Gm13476, zinc finger E-box binding homeobox 2, opposite strand (Zeb2os) / 0.77 / 433424 / “GM13476 isca zincfinger transcription factor. Acts as a transcriptional repressor. Inhibits interleukin-2 (IL-2) gene expression. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell type. Represses E-cadherin promoter and induces an epithelial-mesenchymal transition (EMT) by recruiting SMARCA4/BRG1. Represses BCL6 transcription in the presence of the corepressor CTBP1. Positively regulates neuronal differentiation. Represses RCOR1 transcription activation during neurogenesis. Represses transcription by binding to the E box (5-CANNTG-3).”