Gene Symbol: Id4
Description: inhibitor of DNA binding 4
Alias: Idb4, bHLHb27, DNA-binding protein inhibitor ID-4, inhibitor of differentiation 4
Species: mouse
Products:     Id4

Top Publications

  1. Riechmann V, van Crüchten I, Sablitzky F. The expression pattern of Id4, a novel dominant negative helix-loop-helix protein, is distinct from Id1, Id2 and Id3. Nucleic Acids Res. 1994;22:749-55 pubmed
    ..We have isolated and characterized a novel mouse dnHLH gene, designated Id4. The Id4 protein contains a HLH domain highly conserved among the dnHLH proteins from mouse and drosophila...
  2. Mantani A, Hernandez M, Kuo W, Israel M. The mouse Id2 and Id4 genes: structural organization and chromosomal localization. Gene. 1998;222:229-35 pubmed
    ..In this paper, we report the genomic organization of the mouse Id2 and Id4 genes...
  3. Marin Husstege M, He Y, Li J, Kondo T, Sablitzky F, Casaccia Bonnefil P. Multiple roles of Id4 in developmental myelination: predicted outcomes and unexpected findings. Glia. 2006;54:285-96 pubmed
    ..This study addresses the role of the helix-loop-helix protein Id4 in these two events...
  4. Gokhan S, Marin Husstege M, Yung S, Fontanez D, Casaccia Bonnefil P, Mehler M. Combinatorial profiles of oligodendrocyte-selective classes of transcriptional regulators differentially modulate myelin basic protein gene expression. J Neurosci. 2005;25:8311-21 pubmed
    ..e., Olig1 and Olig2, Mash1), associated inhibitory HLH (i.e., Id2 and Id4), high-mobility group domain (i.e., Sox10), and homeodomain (i.e., Nkx2...
  5. Samanta J, Kessler J. Interactions between ID and OLIG proteins mediate the inhibitory effects of BMP4 on oligodendroglial differentiation. Development. 2004;131:4131-42 pubmed
    ..Overexpression of Id4 or Id2 but not Id1 or Id3 in cultured progenitor cells reproduced both the inhibitory effects of BMP4 treatment on ..
  6. Bedford L, Walker R, Kondo T, van Crüchten I, King E, Sablitzky F. Id4 is required for the correct timing of neural differentiation. Dev Biol. 2005;280:386-95 pubmed
    ..Complex intrinsic and extrinsic mechanisms determine neural cell fate during development of the nervous system. Using Id4 deficient mice, we show that Id4 is required for normal development of the central nervous system (CNS), timing ..
  7. Yun K, Mantani A, Garel S, Rubenstein J, Israel M. Id4 regulates neural progenitor proliferation and differentiation in vivo. Development. 2004;131:5441-8 pubmed
    ..Here, we report that Id4 is required for normal brain size, and regulates lateral expansion of the proliferative zone in the developing ..
  8. Hashimoto M, Murata K, Ishida J, Kanou A, Kasuya Y, Fukamizu A. Severe Hypomyelination and Developmental Defects Are Caused in Mice Lacking Protein Arginine Methyltransferase 1 (PRMT1) in the Central Nervous System. J Biol Chem. 2016;291:2237-45 pubmed publisher
    ..Our findings provide evidence that PRMT1 is required for CNS development, especially for oligodendrocyte maturation processes. ..
  9. Chen S, Claus R, Lucas D, Yu L, Qian J, Ruppert A, et al. Silencing of the inhibitor of DNA binding protein 4 (ID4) contributes to the pathogenesis of mouse and human CLL. Blood. 2011;117:862-71 pubmed publisher
    Inhibitor of DNA binding protein 4 (ID4) is a member of the dominant-negative basic helix-loop-helix transcription factor family that lacks DNA binding activity and has tumor suppressor function...

More Information


  1. Tokuzawa Y, Yagi K, Yamashita Y, Nakachi Y, Nikaido I, Bono H, et al. Id4, a new candidate gene for senile osteoporosis, acts as a molecular switch promoting osteoblast differentiation. PLoS Genet. 2010;6:e1001019 pubmed publisher
    ..Among transcription factors that were enriched in the early phase of differentiation, Id4 was identified as a key molecule affecting the differentiation of both cell types...
  2. Chen Y, Wu H, Wang S, Koito H, Li J, Ye F, et al. The oligodendrocyte-specific G protein-coupled receptor GPR17 is a cell-intrinsic timer of myelination. Nat Neurosci. 2009;12:1398-406 pubmed publisher
  3. Best S, Hutt K, Fu N, Vaillant F, Liew S, Hartley L, et al. Dual roles for Id4 in the regulation of estrogen signaling in the mammary gland and ovary. Development. 2014;141:3159-64 pubmed publisher
    The HLH transcriptional regulator Id4 exerts important roles in different organs, including the neural compartment, where Id4 loss usually results in early lethality...
  4. Riechmann V, Sablitzky F. Mutually exclusive expression of two dominant-negative helix-loop-helix (dnHLH) genes, Id4 and Id3, in the developing brain of the mouse suggests distinct regulatory roles of these dnHLH proteins during cellular proliferation and differentiation of t. Cell Growth Differ. 1995;6:837-43 pubmed
    ..5 to 17.5 postcoitus to establish the spatial and temporal expression patterns of Id3 (HLH462) and Id4, a recently isolated fourth member of the mammalian dnHLH gene family...
  5. Kusunoki T, Sugai M, Katakai T, Omatsu Y, Iyoda T, Inaba K, et al. TH2 dominance and defective development of a CD8+ dendritic cell subset in Id2-deficient mice. J Allergy Clin Immunol. 2003;111:136-42 pubmed
    ..Id2 is an indispensable regulator of the TH1/TH2 balance, possibly through the proper development of CD8alpha+ DCs, and could be a novel target to treat allergic diseases. ..
  6. Murad J, Place C, Ran C, Hekmatyar S, Watson N, Kauppinen R, et al. Inhibitor of DNA binding 4 (ID4) regulation of adipocyte differentiation and adipose tissue formation in mice. J Biol Chem. 2010;285:24164-73 pubmed publisher
    Inhibitor of DNA binding 4 (ID4) is a helix-loop-helix protein that heterodimerizes with basic helix-loop-helix transcription factors inhibiting their function...
  7. Moskowitz I, Kim J, Moore M, Wolf C, Peterson M, Shendure J, et al. A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development. Cell. 2007;129:1365-76 pubmed
    ..We conclude that a molecular pathway including Tbx5, Nkx2-5, and Id2 coordinates specification of ventricular myocytes into the ventricular conduction system lineage. ..
  8. Yumoto K, Thomas P, Lane J, Matsuzaki K, Inagaki M, Ninomiya Tsuji J, et al. TGF-?-activated kinase 1 (Tak1) mediates agonist-induced Smad activation and linker region phosphorylation in embryonic craniofacial neural crest-derived cells. J Biol Chem. 2013;288:13467-80 pubmed publisher
    ..The role of Smad-independent TGF-? signaling in craniofacial development is poorly elucidated...
  9. Sun F, Xu Q, Zhao D, Degui Chen C. Id4 Marks Spermatogonial Stem Cells in the Mouse Testis. Sci Rep. 2015;5:17594 pubmed publisher
    ..Here, we generated a knock-in mouse model, Id4-2A-CreERT2-2A-tdTomato, which allowed us to mark Id4-expressing (Id4(+)) cells at different time points in situ and ..
  10. Kee Y, Bronner Fraser M. Id4 expression and its relationship to other Id genes during avian embryonic development. Mech Dev. 2001;109:341-5 pubmed
    We present the sequence and expression pattern of chick Id4 and compare its distribution to that of other vertebrate Id genes...
  11. Jones J, Montcouquiol M, Dabdoub A, Woods C, Kelley M. Inhibitors of differentiation and DNA binding (Ids) regulate Math1 and hair cell formation during the development of the organ of Corti. J Neurosci. 2006;26:550-8 pubmed
    ..These results indicate a key role for Ids in the regulation of expression of Math1 and hair cell differentiation in the developing cochlea. ..
  12. Zhang T, OATLEY J, Bardwell V, Zarkower D. DMRT1 Is Required for Mouse Spermatogonial Stem Cell Maintenance and Replenishment. PLoS Genet. 2016;12:e1006293 pubmed publisher
    ..Committed progenitor cells expressing Ngn3 normally do not contribute to SSCs marked by the Id4-Gfp transgene, but do so when spermatogonia are chemically depleted using busulfan...
  13. Loomes K, Stevens S, O Brien M, Gonzalez D, Ryan M, Segalov M, et al. Dll3 and Notch1 genetic interactions model axial segmental and craniofacial malformations of human birth defects. Dev Dyn. 2007;236:2943-51 pubmed
    ..Thus, Dll3-Notch1 double heterozygous mice model human congenital scoliosis and craniofacial disorders. ..
  14. Boualia S, Gaitan Y, Tremblay M, Sharma R, Cardin J, Kania A, et al. A core transcriptional network composed of Pax2/8, Gata3 and Lim1 regulates key players of pro/mesonephros morphogenesis. Dev Biol. 2013;382:555-66 pubmed publisher
  15. Duffield G, Watson N, Mantani A, Peirson S, Robles Murguia M, Loros J, et al. A role for Id2 in regulating photic entrainment of the mammalian circadian system. Curr Biol. 2009;19:297-304 pubmed publisher
    Inhibitor of DNA binding genes (Id1-Id4) encode helix-loop-helix (HLH) transcriptional repressors associated with development and tumorigenesis [1, 2], but little is known concerning the function(s) of these genes in normal adult animals...
  16. Du Y, Yip H. The expression and roles of inhibitor of DNA binding helix-loop-helix proteins in the developing and adult mouse retina. Neuroscience. 2011;175:367-79 pubmed publisher
    ..5 through 16.5. Id4 expression began at E18.5. By E18...
  17. Peddada S, Yasui D, LaSalle J. Inhibitors of differentiation (ID1, ID2, ID3 and ID4) genes are neuronal targets of MeCP2 that are elevated in Rett syndrome. Hum Mol Genet. 2006;15:2003-14 pubmed
    ..all four known members of the inhibitors of differentiation or inhibitors of DNA-binding (ID1, ID2, ID3 and ID4) subfamily of helix-loop-helix genes as novel neuronal targets of MeCP2...
  18. Zhou C, Pinson K, Pleasure S. Severe defects in dorsal thalamic development in low-density lipoprotein receptor-related protein-6 mutants. J Neurosci. 2004;24:7632-9 pubmed
    ..This study provides compelling in vivo evidence that thalamic development requires normal activity of the LRP6-mediated canonical Wnt signaling pathway. ..
  19. Walcher T, Xie Q, Sun J, Irmler M, Beckers J, Oztürk T, et al. Functional dissection of the paired domain of Pax6 reveals molecular mechanisms of coordinating neurogenesis and proliferation. Development. 2013;140:1123-36 pubmed publisher
    ..Thus, Pax6 achieves its key roles in the developing forebrain by utilizing particular subdomains to coordinate patterning, neurogenesis and proliferation simultaneously. ..
  20. Paschaki M, Schneider C, Rhinn M, Thibault Carpentier C, Dembele D, Niederreither K, et al. Transcriptomic analysis of murine embryos lacking endogenous retinoic acid signaling. PLoS ONE. 2013;8:e62274 pubmed publisher
    ..Overall, these data give an overview of the gene expression changes resulting from embryonic RA deficiency, and provide new candidate genes and pathways that may help understanding retinoid-dependent molecular events. ..
  21. Britz O, Mattar P, Nguyen L, Langevin L, Zimmer C, Alam S, et al. A role for proneural genes in the maturation of cortical progenitor cells. Cereb Cortex. 2006;16 Suppl 1:i138-51 pubmed
    ..Taken together, these data support a model whereby Ngn2 and Mash1 function together to regulate the zonal distribution of progenitors in the developing neocortex. ..
  22. Hirai S, Miwa A, Ohtaka Maruyama C, Kasai M, Okabe S, Hata Y, et al. RP58 controls neuron and astrocyte differentiation by downregulating the expression of Id1-4 genes in the developing cortex. EMBO J. 2012;31:1190-202 pubmed publisher
    ..Here, we report that a transcriptional factor, RP58, negatively regulates all four Id genes (Id1-Id4) in developing cerebral cortex...
  23. Yu L, Liu C, Vandeusen J, Becknell B, Dai Z, Wu Y, et al. Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia. Nat Genet. 2005;37:265-74 pubmed
    ..We also identified Idb4 as a putative tumor-suppressor gene that is methylated in most mouse and human leukemias but in only a minority of ..
  24. Junankar S, Baker L, Roden D, Nair R, Elsworth B, Gallego Ortega D, et al. ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype. Nat Commun. 2015;6:6548 pubmed publisher
    ..In this study, we show that inhibitor of differentiation 4 (ID4) is a key regulator of mammary stem cell self-renewal and marks a subset of BLBC with a putative ..
  25. Weng H, Kim C, Valavanis C, Wang Z, Schwartz L. Acheron, an novel LA antigen family member, binds to CASK and forms a complex with Id transcription factors. Cell Mol Biol Lett. 2009;14:273-87 pubmed publisher
    ..Taken together, these data suggest a mechanism by which Acheron may regulate development and pathology. ..
  26. Dong J, Huang S, Caikovski M, Ji S, McGrath A, Custorio M, et al. ID4 regulates mammary gland development by suppressing p38MAPK activity. Development. 2011;138:5247-56 pubmed publisher
    ..regulates cell proliferation and differentiation in many different developmental pathways, but the functions of ID4 in mammary development are unknown...
  27. Borinstein S, Conerly M, Dzieciatkowski S, Biswas S, Washington M, Trobridge P, et al. Aberrant DNA methylation occurs in colon neoplasms arising in the azoxymethane colon cancer model. Mol Carcinog. 2010;49:94-103 pubmed publisher
    ..Zik1 and Gja9 demonstrated cancer-specific aberrant DNA methylation, whereas, Cdkn2a/p16, Igfbp3, Mgmt, Id4, and Cxcr4 were methylated in both the AOM tumors and normal colon mucosa...
  28. Miyashita Lin E, Hevner R, Wassarman K, Martinez S, Rubenstein J. Early neocortical regionalization in the absence of thalamic innervation. Science. 1999;285:906-9 pubmed
    ..This provides evidence that patterning mechanisms intrinsic to the neocortex specify the basic organization of its functional subdivisions. ..
  29. Israel M, Hernandez M, Florio M, Andres Barquin P, Mantani A, Carter J, et al. Id gene expression as a key mediator of tumor cell biology. Cancer Res. 1999;59:1726s-1730s pubmed
    ..These findings suggest that not only the inappropriate proliferation of tumors but also the anaplastic characteristics that contribute to their malignant behavior may be regulated by Id gene expression. ..
  30. Stewart H, Zoidl G, Rossner M, Brennan A, Zoidl C, Nave K, et al. Helix-loop-helix proteins in Schwann cells: a study of regulation and subcellular localization of Ids, REB, and E12/47 during embryonic and postnatal development. J Neurosci Res. 1997;50:684-701 pubmed
    ..In this study, we have analyzed the expression of the dominant negative HLH genes, Id1 to Id4 and the class A gene REB, during Schwann cell development...
  31. Huang J, Vogel G, Yu Z, Almazan G, Richard S. Type II arginine methyltransferase PRMT5 regulates gene expression of inhibitors of differentiation/DNA binding Id2 and Id4 during glial cell differentiation. J Biol Chem. 2011;286:44424-32 pubmed publisher
    ..progenitor and C6 glioma cells expressed high levels of the inhibitors of differentiation/DNA binding, Id2 and Id4, known repressors of glial cell differentiation...
  32. Bonilla Claudio M, Wang J, Bai Y, Klysik E, Selever J, Martin J. Bmp signaling regulates a dose-dependent transcriptional program to control facial skeletal development. Development. 2012;139:709-19 pubmed publisher
    ..These data support the hypothesis that Bmp signaling regulates craniofacial skeletal development by balancing self-renewal and differentiation pathways in CNC progenitors. ..
  33. van Crüchten I, Cinato E, Fox M, King E, Newton J, Riechmann V, et al. Structure, chromosomal localisation and expression of the murine dominant negative helix-loop-helix Id4 gene. Biochim Biophys Acta. 1998;1443:55-64 pubmed
    ..In order to establish the molecular and functional properties of Id4, we analysed structure, chromosomal localisation and expression of the murine Id4 gene...
  34. Jen Y, Manova K, Benezra R. Each member of the Id gene family exhibits a unique expression pattern in mouse gastrulation and neurogenesis. Dev Dyn. 1997;208:92-106 pubmed
    ..5 dpc onward, whereas Id2 is expressed in tissues derived from trophoblasts. Id4 expression is absent during this period of development...
  35. Jen Y, Manova K, Benezra R. Expression patterns of Id1, Id2, and Id3 are highly related but distinct from that of Id4 during mouse embryogenesis. Dev Dyn. 1996;207:235-52 pubmed
    ..1994] Nucleic Acids Res. 22:749-755). Currently, there are four members in the dnHLH family, Id1, Id2, Id3, and Id4. In this report, we have performed a detailed comparative in situ hybridization analysis to examine their ..
  36. Loveys D, Streiff M, Kato G. E2A basic-helix-loop-helix transcription factors are negatively regulated by serum growth factors and by the Id3 protein. Nucleic Acids Res. 1996;24:2813-20 pubmed
    ..Four murine cDNAs were identified in the screen, all of which encode helix-loop-helix proteins: E12, E47, ALF1 and Id4. Co-immunoprecipitation assays confirm that Id3 interacts with E12, E47 and two alternative splice products of ALF1 ..
  37. Oatley M, Kaucher A, Racicot K, Oatley J. Inhibitor of DNA binding 4 is expressed selectively by single spermatogonia in the male germline and regulates the self-renewal of spermatogonial stem cells in mice. Biol Reprod. 2011;85:347-56 pubmed publisher
    ..We show that in the mouse male germline the transcriptional repressor ID4 is expressed by a subpopulation of undifferentiated spermatogonia and selectively marks A(single) spermatogonia...
  38. Mukhopadhyay P, Rezzoug F, Webb C, Pisano M, Greene R. Suppression of chondrogenesis by Id helix-loop-helix proteins in murine embryonic orofacial tissue. Differentiation. 2009;77:462-72 pubmed publisher
    ..In the present study, the mRNA and protein expression patterns of Id1, Id2, Id3 and Id4 were examined in developing murine orofacial tissue in vivo, as well as in murine embryonic maxillary mesenchymal ..
  39. Helsel A, Yang Q, Oatley M, Lord T, Sablitzky F, Oatley J. ID4 levels dictate the stem cell state in mouse spermatogonia. Development. 2017;144:624-634 pubmed publisher
    ..Here we used an Id4-eGfp reporter mouse to discover that EGFP intensity is predictive of the subsets, with the ID4-EGFPBright
  40. Sharma P, Knowell A, Chinaranagari S, Komaragiri S, Nagappan P, Patel D, et al. Id4 deficiency attenuates prostate development and promotes PIN-like lesions by regulating androgen receptor activity and expression of NKX3.1 and PTEN. Mol Cancer. 2013;12:67 pubmed publisher
    b>Inhibitor of differentiation 4 (Id4), a member of the helix-loop-helix family of transcriptional regulators has emerged as a tumor suppressor in prostate cancer...