TRANSCRIPTION FACTORS IN STP
(see also Main nuclear receptors and tools to analyze transcription)
 
 
TF name
expressed in ...
activators
inhibitors
up-regulated genes
down-regulated genes
pre-initiation complex (PIC) / general transcription factors (GTFs) 
  • TFIID
  • TFIIB
  • TFIIF
  • TFIIE
  • all cells
    RNA polymerase I
    RNA polymerase II (initiation of transcription by RNA polymerase II requires the activities of > 70 polypeptides)  amatoxins
    RNA polymerase III amatoxins
    TFIIH
  • DNA helicase 
  • cyclin H 
  • CDK7 (activates RNA polymerase II)
  • XP II / XPB
  • XP IV / XPD / XP VIII / XPH
  • YDR079c-a / TFB5 / GTF2H5 / tricothiodystrophy disorder (TTD-A)ref1, ref2
  • TFIIJ
    cAMP responsive element binding (CREB) protein
    Web resources : CREB Target Gene Database from Marc Montminy of the Salk Institute in La Jolla, California
    CREB1 cAMP-responsive element (CRE) (5'-TGACCTCA-3')-containing genes : 
    CREB2
    nuclear factor Y (NF-Y) : a histone-like CCAAT-binding protein that cooperates with E2 factors (E2F) to regulate transcription of many cell cycle genes. NF-Y is the prototype of a constitutive, ubiquitous factor that pre-sets the promoter architecture for other regulatory proteins to access it; heterotrimer 
    AP1
    • Jun family members form low-affinity homodimers or high-affinity heterodimers (via LZ) that recognize a TGAGTCA consensus DNA sequence
    • Fos family members are unable to homodimerize, augment transcriptional activation by forming heterodimers with Jun family members
    ROS 
    H2O2
    Cys252 reduction
    PNRI-299  IL-4
    IL-5
    IL-13
    Muc5B
    HO-1
    nuclear factor activator of T cells (NFAT) NFAT1 / NFATc1 T cells 
    NFAT2 / NFATc2 T cells
    NFAT3 / NFATc3
    NFAT4 / NFATc4 T cells
    NFAT5 / tonicity enhancer binding protein (TonEBP) : deletion of exons 6 and 7 of NFAT5 eliminated its ability to bind DNA and function as a TF T cells, renal medullary epithelial cells, all tissues of developing embryos (expecially brain and heart) hypertonicity SLC5A3 / sodium/myoinositol transporter
    SLC6A12 / betaine/g-aminobutyric acid transporter
    SLC38A2 / ATA2
    TNF-a
    LT-b
    nuclear factor k B (NFkB) is a homodimer or  heterodimer of the following 5 subunits from the Rel family (containing Rel homology (RH) domains) : 
    • p50NFkB-1 (p105 precursor)
    • p52NFkB-2 (p100 precursor)
    • p65RelA (ARF causes RELA to associate with HDAC1, which repress es transcription of RELA, and directly represses the transcriptional activity of RELA in response to the oncogene BCR-ABL)
    • c-Rel (homolog of v-Rel)
    • RelB (heterodimerizes only with p50NFkB-1 or p52NFkB-2)
    • dorsal (in Drosophila melanogaster)
    IkBz / molecule possessing ankyrin repeats induced by lipopolysaccharide (MAIL) / INAP is an ankyrin-repeat-containing nuclear protein that is highly homologous to the IkB family member Bcl-3. Transcription of IkBz is rapidly induced by stimulation with TLR ligands and IL-1. IkBz is indispensable for the expression of a subset of genes (including IL-6, Il12b and Csf2) activated in TLR/IL-1R signalling pathways, but not in response to TNF-a. Endogenous IkBz specifically associates with the p50 subunit of NF-kB. Given that the lipopolysaccharide-induced transcription of IkBz occurs earlier than transcription of these genes, some TLR/IL-1R-mediated responses may be regulated in a gene expression process of at least 2 steps that requires inducible IkBzref
    caffeic acid phenetyl ester (CAPE) 
    parthenolide 
    2-hydroxy-4-trifluoromethylbenzoic acid (HTB) 
    1-pyrrolidinecarbodithioic acid / pyrrolidine dithiocarbamate (PDTC) 
    deoxyspergualin (DSG) (inhibitor of translocation)
    IL-1b
    IL-4
    IL-5
    IL-9
    IL-15
    TNF-a
    CCL-5 / RANTES
    CCL-7 / MCP-3
    CCL11 / eotaxin
    CD54 / ICAM-1
    CD106 / VCAM-1 / INCAM-110
    COX-2
    E2F family E2F1
    E2F2
    E2F3
    E2F4
    E2F5
    E2F6
    signal transducer and activator of transcription (STAT)
    STAT1
    STAT2 [the 79-kD protein encoded by M27 gene of mouse cytomegalovirus (MCMV) selectively binds and down-regulates STAT-2. The absence of pM27 conferred MCMV susceptibility to type I IFNs (a/ß), but it had a much more dramatic effect on type II IFNs (g) in vitro and in vivo. A comparative analysis of M27+ and M27 MCMV revealed that the antiviral efficiency of IFN-g was partially dependent on the synergistic action of type I IFNs that required STAT2. Moreover, STAT2 was directly activated by IFN-g. This effect required IFN receptor expression and was independent of type I IFNs. IFN-g induced increasing levels of tyrosine-phosphorylated STAT2 in M27– MCMV-infected cells that were essential for the antiviral potency of IFN-g. pM27 represents a new strategy for simultaneous evasions from types I and II IFNs, and it documents an unknown biological significance for STAT2 in antiviral IFN-g responsesref]
    STAT3 requires phosphorylation on Ser727 and Tyr705 to be transcriptionally active: enhances the efficiency of its own Ser-727 phosphorylation by acting as a scaffold for the TAK1-NLK kinases, specifically in the IL-6R gp130 YXXQ motif-derived pathwayref. The truncated form of STAT3b lacks the carboxy-terminal transcruptional activation domain and is thought to be dominant negative to the full-length form STAT3a in transducing signals through cytokine receptors. But new research has shown that STAT3b can carry out the essential developmental functions of STAT3a and rescue the embryonic lethality of complete STAT3 deletion, and can also activate transcrption of certain target genes, such as those encoding APPs in the liver. However, STAT3b cannot compensate for all functions of full-length STAT3a, such as regulating signalling though the IL-6R, indicating that the 2 forms are non-redundantref. In response to cytokine treatment, Stat3 is also acetylated by p300 on a single lysine residue, Lys685 (reversible by type I histone deacetylase (HDAC)), critical for Stat3 to form stable dimers required for cytokine-stimulated DNA binding and transcriptional regulation, to enhance transcription of cell growth–related genes, and to promote cell cycle progression in response to treatment with oncostatin Mref
    STAT4
    STAT5 
    STAT6 TNF-a
    regulatory factor X (RFX) family  RFX1
    RFX2
    RFX3
    RFX4
    RFX5
    RFX-B / ANK
    RFXAP
    GATA family GATA1
    GATA2
    GATA3
    GATA4
    GATA5
    GATA6
    interferon regulatory factor (IRF) family IRF1 activates the expression of IFN-a and ß and maps to chromosome 5q31.1. As it is thought to act as a tumor suppressor gene, its role in the pathologic consequences of the 5q– syndrome is under active investigation
    IRF2 binds to a promoter element shared by IFN-a and ß and many interferon-inducible genes. Unlike IRF-1, which stimulates such genes, IRF-2 represses transcription at the site. It is felt that the ratio of IRF-1 to IRF-2 might be a critical event in the regulation of cellular proliferation. 
    IRF3
    IRF4
    IRF5
    IRF6
    IRF7
    IRF8
    IRF9 / interferon-stimulated transcription factor 3, gamma  48 kDa (ISGF3G)
    ETS family
    HIF-1 is a heterodimeric bHLH Per/ARNT/Sim (PAS)-domain TF 
    hypoxia-responsive element (HRE) (5'-RCGTG-3')-containing genes: 
    CCAAT/enhancer binding protein (C/EBP) b (CEBPB) / NF-IL6 is a bLZ
    CBP/p300 contain 2 transcriptional adapter zinc-binding (TAZ) motifs 
    • TAZ1 motif corresponds to cysteine/histidine-rich domain-1 (the CH1 domain)
    • TAZ2 domain and the zz zinc-binding domain together make up cysteine/histidine-rich domain-3 (the CH3 domain)
    The TAZ1 and TAZ2 domains each bind 3 Zn2+ ions though HCCC motifs that are completely conserved across all species sequenced to date.
    undetermined hypoxia-inducible TFs DDIT3 / GADD153
    ornithine decarboxylase (ODC)
    p27
    high motility group (HMG) TCF-1
    TCF-3
    TCF-4
    LEF1
    high mobility group AT-hook 1 (HMGA1 / HMG I(Y))
    basic helix-loop-helix (bHLH) family : dimerize through a domain containing 2 a helical regions separated by a loop structure microphthalmia-associated transcription factor (MITF) E-box (CANNTG) containing genes : 
    c-MYC binds DNA as a heterodimer with MAX : it is believed to regulate the expression of 15% of all genes WRN
    myogenic : 
    transcription factor 3 (TCF3) / E2A immunoglobulin enhancer-binding factor E12/E47 of the immunoglobulin promoter
    musculin (MSC) / activated B-cell factor 1 (ABF1) / MYO-R : the predicted 218-amino acid protein contains a bHLH motif, a putative nuclear localization signal, a glycine-rich region, and a stretch of acidic residues. MSC is capable of binding an E-box element either as a homodimer or as a heterodimer with E2A in vitro, and forms heterodimers with E2A proteins in vivo. MSC contains a transcriptional repression domain and is capable of inhibiting the transactivation capability of E47, an E2A protein, in mammalian cells. MSC is a downstream target of the B-cell receptor signal transduction pathway. It is expressed only in skeletal muscle precursors and adult kidney side population (SP) cells in the renal interstitial space. Musculin/MyoR+ cells were decreased in ARF, but infusion of kidney SP cells increased musculin/MyoR+ cells and improved renal function. Kidney SP cells in reversible ARF expressed a high level of renoprotective factors and LIF, but not in irreversible CRF. In cultured kidney SP cells, LIF stimulated gene expression of renoprotective factors, and down-regulation of musculin/MyoR augmented LIF-induced gene expression.ref.
    helix-loop-helix (HLH) T-cell acute lymphocytic leukemia 1 (TAL1) / stem cell leukemia (SCL) : this proto-oncogene, first identified in a stem cell leukemia at the site of t(1;14), is a member of the  group of transcriptionally active proteins. The association of t(1;14) with up to 25% of T cell ALL suggests that its ectopic expression is associated with transformation  erythroid and mast cell lineages but not in T cells
    ETV6 / TEL : fused to the PDGFß-receptor in CMML t(5:12) and to other genes in AML or MDS. Like most other translocation oncogenes, the mechanism of leukemogenesis is unknown. More recently, a TEL/AML1 fusion gene representing a t(12;21) has been found in a large number of cases of childhood ALL. As the translocation is not detected by routine cytogenetics, molecular analysis (FISH, etc.) is required to identify this favorable chromosomal rearrangement. 
    inhibitor of DNA binding (ID) family, members of which are transcriptional regulators that contain a HLH domain but not a basic domain : members of the ID family inhibit the functions of basic helix-loop-helix transcription factors in a dominant-negative manner by suppressing their heterodimerization partners through the HLH domains. This protein may play a role in negatively regulating cell differentiation. A pseudogene has been identified for this gene
    nuclear factor (erythroid-derived 2)-like 3 (NFE2L3)
    basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor family sterol response element regulatory proteins (SREBP) LDLR
    basic leucine zipper (bLZ) nuclear factor erythroid-derived 2 (NF-E2) family NF-E2-related factor 2 (NRF2) / GA binding protein transcription factor, a subunit (GABPA) 60 kDaref1, ref2 antioxidant response element (ARE)-containing genes : 
    myocyte enhancer factor-2 (MEF2) family MEF2A
    MEF2B
    MEF2C
    MEF2D
    homeobox transcription factor Pou domain, class 5, transcription factor 1 (POU5F1) / octamer-binding transcription factor 3 (Oct3/4) ES cells, type A spermatogonia in the adult male (levels of expression are correlated with maturity), GCTs
    Nanog (from the Celtic "Tir nan Og" meaning "Land of the Ever Young") preimplantation embryos (from the morula stage through to the epiblast), primordial germ cells (PGC), various tumors, undifferentiated ES cells
    Interferon-consensus-sequence-binding protein 1 (ICSBP1)
    core binding factor b (CBFB) : a family of heterodimeric transcription factors containing a common ß subunit, CBFß, and one of 3 CBF subunits : CBFß increases the affinities of the CBF subunits for DNA. Mice lacking CBFß or AML1 fail to develop definitive hematopoiesis. 
    C-MYB is expressed primarily in immature hematopoietic cells and declines as cells differentiate. Forced expression of c-myb blocks hematopoietic differentiation. Clinically, high levels of myb are noted in acute leukemia, and such patients are less likely to enter remission or tend to have a short remission duration. 
    helix-turn-helix (HTH) : this family of transcriptionally active proteins depends on the helix-turn-helix motif for dimerization Homeobox (Hox) genes : first identified as master switch transcriptional regulators of early development. Hox genes control body segmentation and more recently have been found to play a role in regulating hematopoietic stem cell survival and proliferation. 
    zinc finger (ZnF) domain proteins : a large family of transcriptionally active proteins that includes the steroid hormone receptors. The presence of conserved histidine and cysteine residues allows chelation of a zinc atom and results in the formation of a loop structure called the zinc finger domain.  Yin Yang 1 (YY1)
    early growth response 1 (EGR-1) / ZIF-268 (ZnF expressed in hypoxic mononuclear phagocytes) tissue factor (TF)ref1, ref2, ref3, ref4, ref5, ref6
    forkhead family FOXP1
    FOXP2
    FOXP3 CD4+ regulatory T cells

    JAK/STAT family mutants and their associated phenotypes :


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