Gene Symbol: Chd4
Description: chromodomain helicase DNA binding protein 4
Alias: 9530019N15Rik, AA617397, BC005710, D6Ertd380e, Mi-2beta, mKIAA4075, chromodomain-helicase-DNA-binding protein 4, CHD-4, Mi-2 beta
Species: mouse
Products:     Chd4

Top Publications

  1. Williams C, Naito T, Arco P, Seavitt J, Cashman S, De Souza B, et al. The chromatin remodeler Mi-2beta is required for CD4 expression and T cell development. Immunity. 2004;20:719-33 pubmed
    ..These findings provide important insights into the regulation of CD4 expression during T cell development and define a role for Mi-2beta in gene activation. ..
  2. Srinivasan R, Mager G, Ward R, Mayer J, Svaren J. NAB2 represses transcription by interacting with the CHD4 subunit of the nucleosome remodeling and deacetylase (NuRD) complex. J Biol Chem. 2006;281:15129-37 pubmed modulated by at least two repression domains within NAB2, one of which uniquely requires interaction with the CHD4 (chromodomain helicase DNA-binding protein 4) subunit of the NuRD (nucleosome remodeling and deacetylase) chromatin ..
  3. Verstappen G, van Grunsven L, Michiels C, Van de Putte T, Souopgui J, Van Damme J, et al. Atypical Mowat-Wilson patient confirms the importance of the novel association between ZFHX1B/SIP1 and NuRD corepressor complex. Hum Mol Genet. 2008;17:1175-83 pubmed publisher
    ..This is the first study providing mechanistic insight into the aberrant function of a single domain of the multi-domain protein ZFHX1B/SIP1 in human disease. ..
  4. Zhang J, Jackson A, Naito T, Dose M, Seavitt J, Liu F, et al. Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis. Nat Immunol. 2011;13:86-94 pubmed publisher
    ..Thus, release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally opposing epigenetic and genetic networks. ..
  5. Reynolds N, Salmon Divon M, Dvinge H, Hynes Allen A, Balasooriya G, Leaford D, et al. NuRD-mediated deacetylation of H3K27 facilitates recruitment of Polycomb Repressive Complex 2 to direct gene repression. EMBO J. 2012;31:593-605 pubmed publisher
  6. Polo S, Kaidi A, Baskcomb L, Galanty Y, Jackson S. Regulation of DNA-damage responses and cell-cycle progression by the chromatin remodelling factor CHD4. EMBO J. 2010;29:3130-9 pubmed publisher
    The chromatin remodelling factor chromodomain helicase DNA-binding protein 4 (CHD4) is a catalytic subunit of the NuRD transcriptional repressor complex...
  7. Harju Baker S, Costa F, Fedosyuk H, Neades R, Peterson K. Silencing of Agamma-globin gene expression during adult definitive erythropoiesis mediated by GATA-1-FOG-1-Mi2 complex binding at the -566 GATA site. Mol Cell Biol. 2008;28:3101-13 pubmed publisher
  8. Kim J, Sif S, Jones B, Jackson A, Koipally J, Heller E, et al. Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes. Immunity. 1999;10:345-55 pubmed
    ..We propose that the restructuring of chromatin is a key aspect of Ikaros function in lymphocyte differentiation. ..
  9. Hosokawa H, Tanaka T, Suzuki Y, Iwamura C, Ohkubo S, Endoh K, et al. Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity. Proc Natl Acad Sci U S A. 2013;110:4691-6 pubmed publisher
    ..Here we show that chromodomain helicase DNA-binding protein 4 (Chd4) forms a complex with Gata3 in Th2 cells that both activates Th2 cytokine transcription and represses the Th1 ..

More Information


  1. Yamada T, Yang Y, Hemberg M, Yoshida T, Cho H, Murphy J, et al. Promoter decommissioning by the NuRD chromatin remodeling complex triggers synaptic connectivity in the mammalian brain. Neuron. 2014;83:122-34 pubmed publisher
    ..We report that depletion of the NuRD complex by in vivo RNAi and conditional knockout of the core NuRD subunit Chd4 profoundly impairs the establishment of granule neuron parallel fiber/Purkinje cell synapses in the rodent ..
  2. Kashiwagi M, Morgan B, Georgopoulos K. The chromatin remodeler Mi-2beta is required for establishment of the basal epidermis and normal differentiation of its progeny. Development. 2007;134:1571-82 pubmed
    ..Mi-2beta is however essential for the reprogramming of basal cells to the follicular and, subsequently, hair matrix fates. ..
  3. Gómez del Arco P, Koipally J, Georgopoulos K. Ikaros SUMOylation: switching out of repression. Mol Cell Biol. 2005;25:2688-97 pubmed
    ..These studies reveal a new dynamic way by which Ikaros-mediated gene repression is controlled by SUMOylation. ..
  4. Curtis C, Griffin C. The chromatin-remodeling enzymes BRG1 and CHD4 antagonistically regulate vascular Wnt signaling. Mol Cell Biol. 2012;32:1312-20 pubmed publisher
    ..We have now generated embryos lacking the chromatin-remodeling enzyme Chd4 in vascular endothelial cells. Unlike Brg1 mutants, Chd4 mutant embryos had normal yolk sac vascular morphology...
  5. Hung H, Kohnken R, Svaren J. The nucleosome remodeling and deacetylase chromatin remodeling (NuRD) complex is required for peripheral nerve myelination. J Neurosci. 2012;32:1517-27 pubmed publisher
    ..Chromodomain helicase DNA-binding protein 4 (Chd4) is the core catalytic subunit of the nucleosome remodeling and deacetylase (NuRD) chromatin remodeling complex...
  6. Naito T, Gómez del Arco P, Williams C, Georgopoulos K. Antagonistic interactions between Ikaros and the chromatin remodeler Mi-2beta determine silencer activity and Cd4 gene expression. Immunity. 2007;27:723-34 pubmed
    ..Thus, concomitant interactions between functionally opposing chromatin-regulating machineries are an important mode of gene regulation during lineage determination. ..
  7. Rodriguez P, Bonte E, Krijgsveld J, Kolodziej K, Guyot B, Heck A, et al. GATA-1 forms distinct activating and repressive complexes in erythroid cells. EMBO J. 2005;24:2354-66 pubmed
    ..Based on these findings, we suggest a model for the different roles of GATA-1 in erythroid differentiation. ..
  8. Yoshida T, Hazan I, Zhang J, Ng S, Naito T, Snippert H, et al. The role of the chromatin remodeler Mi-2beta in hematopoietic stem cell self-renewal and multilineage differentiation. Genes Dev. 2008;22:1174-89 pubmed publisher
    ..Thus, Mi-2beta provides the hematopoietic system with immune cell capabilities as well as with an extensive regenerative capacity. ..
  9. Costa F, Fedosyuk H, Chazelle A, Neades R, Peterson K. Mi2? is required for ?-globin gene silencing: temporal assembly of a GATA-1-FOG-1-Mi2 repressor complex in ?-YAC transgenic mice. PLoS Genet. 2012;8:e1003155 pubmed publisher
  10. Ma P, Lin S, Bartolomei M, Schultz R. Metastasis tumor antigen 2 (MTA2) is involved in proper imprinted expression of H19 and Peg3 during mouse preimplantation development. Biol Reprod. 2010;83:1027-35 pubmed publisher
    ..domain protein 3 (MBD3), histone deacetylases 1 and 2 (HDACs 1 and 2), and chromodomain helicase DNA-binding protein 4 (CHD4). Taken together, our results support a role for MTA2 within the NuRD complex in genomic imprinting.
  11. Gowher H, Brick K, Camerini Otero R, Felsenfeld G. Vezf1 protein binding sites genome-wide are associated with pausing of elongating RNA polymerase II. Proc Natl Acad Sci U S A. 2012;109:2370-5 pubmed publisher
    ..We further show that Vezf1 interacts with Mrg15/Mrgbp, a protein that recognizes H3K36 trimethylation, consistent with the role of histone modifications at alternatively spliced sites. ..
  12. Singh A, Foley J, Rubino M, Boyle M, Tandon A, Shah R, et al. Brg1 Enables Rapid Growth of the Early Embryo by Suppressing Genes That Regulate Apoptosis and Cell Growth Arrest. Mol Cell Biol. 2016;36:1990-2010 pubmed publisher
    ..Using P19 cells, we show that Brg1 and CHD4 (chromodomain helicase DNA binding protein 4) coordinate to control target gene expression...
  13. Sparmann A, Xie Y, Verhoeven E, Vermeulen M, Lancini C, Gargiulo G, et al. The chromodomain helicase Chd4 is required for Polycomb-mediated inhibition of astroglial differentiation. EMBO J. 2013;32:1598-612 pubmed publisher
    ..In addition, we identify the chromodomain helicase DNA-binding protein 4 (Chd4) as a critical interaction partner of Ezh2 required specifically for PcG-mediated suppression of the key astrogenic ..
  14. Bottardi S, Zmiri F, Bourgoin V, Ross J, Mavoungou L, Milot E. Ikaros interacts with P-TEFb and cooperates with GATA-1 to enhance transcription elongation. Nucleic Acids Res. 2011;39:3505-19 pubmed publisher
    ..Our results show that Ikaros exerts dual functionality during gene activation, by promoting efficient transcription initiation and elongation. ..
  15. O Shaughnessy Kirwan A, Signolet J, Costello I, Gharbi S, Hendrich B. Constraint of gene expression by the chromatin remodelling protein CHD4 facilitates lineage specification. Development. 2015;142:2586-97 pubmed publisher
    ..Here, we investigate how the chromatin remodelling protein CHD4 facilitates the first lineage decision in mammalian embryogenesis...
  16. Johnson D, Lovett J, Hirsch M, Xia F, Chen J. NuRD complex component Mi-2beta binds to and represses RORgamma-mediated transcriptional activation. Biochem Biophys Res Commun. 2004;318:714-8 pubmed
    ..A yeast two-hybrid screen with Y190 yeast cells under stringent conditions resulted in the identification of CHD4, also known as Mi-2beta, as a RORgamma-interacting protein. This interaction was confirmed by GST pull-down assays...
  17. Devilbiss A, Boyer M, Bresnick E. Establishing a hematopoietic genetic network through locus-specific integration of chromatin regulators. Proc Natl Acad Sci U S A. 2013;110:E3398-407 pubmed publisher
    ..We propose a coregulator matrix model in which distinct combinations of chromatin regulators are required at different GATA-1 target genes, and the unique attributes of the target loci mandate these combinations. ..
  18. Ling T, Xie W, Luo M, Shen M, Zhu Q, Zong L, et al. CHD4/NuRD maintains demethylation state of rDNA promoters through inhibiting the expression of the rDNA methyltransferase recruiter TIP5. Biochem Biophys Res Commun. 2013;437:101-7 pubmed publisher
    ..Thus, NuRD is able to control methylation status of rDNA promoters through crosstalking with NoRC complex. ..
  19. Nitarska J, Smith J, Sherlock W, Hillege M, Nott A, Barshop W, et al. A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development. Cell Rep. 2016;17:1683-1698 pubmed publisher
    ..Whereas CHD4 promotes the early proliferation of progenitors, CHD5 facilitates neuronal migration and CHD3 ensures proper layer ..
  20. Harker N, Garefalaki A, Menzel U, Ktistaki E, Naito T, Georgopoulos K, et al. Pre-TCR signaling and CD8 gene bivalent chromatin resolution during thymocyte development. J Immunol. 2011;186:6368-77 pubmed publisher
    ..Differential binding of Ikaros, NuRD, and heterochromatin protein 1? on the locus during these processes may participate in the complex regulation of CD8. ..
  21. Kashiwagi M, Hosoi J, Lai J, BRISSETTE J, Ziegler S, Morgan B, et al. Direct control of regulatory T cells by keratinocytes. Nat Immunol. 2017;18:334-343 pubmed publisher
    ..Thus, in addition to their well-characterized role in pro-inflammatory responses, keratinocytes also directly support immune-suppressive responses that are critical for re-establishing organismal homeostasis. ..
  22. Sperlazza J, Rahmani M, Beckta J, Aust M, Hawkins E, Wang S, et al. Depletion of the chromatin remodeler CHD4 sensitizes AML blasts to genotoxic agents and reduces tumor formation. Blood. 2015;126:1462-72 pubmed publisher
    Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATPase that alters the phasing of nucleosomes on DNA and has recently been implicated in DNA double-stranded break (DSB) repair...
  23. Crosswhite P, Podsiadlowska J, Curtis C, Gao S, Xia L, Srinivasan R, et al. CHD4-regulated plasmin activation impacts lymphovenous hemostasis and hepatic vascular integrity. J Clin Invest. 2016;126:2254-66 pubmed publisher
    The chromatin-remodeling enzyme CHD4 maintains vascular integrity at mid-gestation; however, it is unknown whether this enzyme contributes to later blood vessel or lymphatic vessel development...
  24. Gómez del Arco P, Perdiguero E, Yunes Leites P, Acin Perez R, Zeini M, Garcia Gomez A, et al. The Chromatin Remodeling Complex Chd4/NuRD Controls Striated Muscle Identity and Metabolic Homeostasis. Cell Metab. 2016;23:881-92 pubmed publisher
    ..types depends on epigenetic repression of the alternate lineage gene program by the chromatin remodeling complex Chd4/NuRD...
  25. Low J, Webb S, Silva A, Saathoff H, Ryan D, Torrado M, et al. CHD4 Is a Peripheral Component of the Nucleosome Remodeling and Deacetylase Complex. J Biol Chem. 2016;291:15853-66 pubmed publisher
    ..1 and 2 (HDAC1 and HDAC2), and is defined by the presence of a CHD family remodeling enzyme, most commonly CHD4 (chromodomain helicase DNA-binding protein 4)...
  26. Olias P, Etheridge R, Zhang Y, Holtzman M, Sibley L. Toxoplasma Effector Recruits the Mi-2/NuRD Complex to Repress STAT1 Transcription and Block IFN-?-Dependent Gene Expression. Cell Host Microbe. 2016;20:72-82 pubmed publisher
    ..These findings demonstrate the importance of both IFN-? responses and the ability of pathogens to counteract these defenses. ..
  27. Kwintkiewicz J, Padilla Banks E, Jefferson W, Jacobs I, Wade P, Williams C. Metastasis-associated protein 3 (MTA3) regulates G2/M progression in proliferating mouse granulosa cells. Biol Reprod. 2012;86:1-8 pubmed publisher
    ..In the ovary, MTA3 interacted with NuRD proteins CHD4 and HDAC1 and the core cohesin complex protein RAD21...
  28. Waldron L, Steimle J, Greco T, Gomez N, Dorr K, Kweon J, et al. The Cardiac TBX5 Interactome Reveals a Chromatin Remodeling Network Essential for Cardiac Septation. Dev Cell. 2016;36:262-75 pubmed publisher
    ..Collectively, this work defines a TBX5-NuRD interaction essential to cardiac development and the evolution of the mammalian heart, and when altered may contribute to human CHD. ..
  29. Osman A, van Kol S, Peijnenburg A, Blokland M, Pennings J, Kleinjans J, et al. Proteomic analysis of mouse thymoma EL4 cells treated with bis(tri-n-butyltin)oxide (TBTO). J Immunotoxicol. 2009;6:174-83 pubmed publisher
    ..and in transcription, splicing factor arginine/serine-rich 2 and chromodomain-helicase-DNA binding protein 4 (Chd4), were decreased 2.6- and 4.5 times, respectively. Nuclear RNA helicase II was reduced 2.8-fold...
  30. Zheng Y, Tan X, Pyczek J, Nolte J, Pantakani D, Engel W. Generation and characterization of yeast two-hybrid cDNA libraries derived from two distinct mouse pluripotent cell types. Mol Biotechnol. 2013;54:228-37 pubmed publisher
    ..Finally, we would like to make these cDNA libraries as a resource that can be distributed to the research community. ..
  31. Sillibourne J, Delaval B, Redick S, Sinha M, Doxsey S. Chromatin remodeling proteins interact with pericentrin to regulate centrosome integrity. Mol Biol Cell. 2007;18:3667-80 pubmed
    ..In a yeast two-hybrid screen with pericentrin we identified chromodomain helicase DNA-binding protein 4 (CHD4/Mi2beta). CHD4 is part of the multiprotein nucleosome remodeling deacetylase (NuRD) complex...
  32. D Alesio C, Punzi S, Cicalese A, Fornasari L, Furia L, Riva L, et al. RNAi screens identify CHD4 as an essential gene in breast cancer growth. Oncotarget. 2016;7:80901-80915 pubmed publisher
    ..Among the genes identified in our screening, we deeply investigated the role of Chromodomain Helicase DNA binding Protein 4 (CHD4) in breast cancer tumorigenesis...
  33. Ingram K, Curtis C, Silasi Mansat R, Lupu F, Griffin C. The NuRD chromatin-remodeling enzyme CHD4 promotes embryonic vascular integrity by transcriptionally regulating extracellular matrix proteolysis. PLoS Genet. 2013;9:e1004031 pubmed publisher
    ..Mice lacking endothelial CHD4--a catalytic subunit of NuRD complexes--died at midgestation from vascular rupture...
  34. Jones D, Cowell I, Singh P. Mammalian chromodomain proteins: their role in genome organisation and expression. Bioessays. 2000;22:124-37 pubmed
    ..This article reviews progress made in characterising mammalian chromodomain proteins and emphasises their emerging role in the regulation of gene expression and genome organisation. BioEssays 22:124-137, 2000. ..
  35. Fessing M, Mardaryev A, Gdula M, Sharov A, Sharova T, Rapisarda V, et al. p63 regulates Satb1 to control tissue-specific chromatin remodeling during development of the epidermis. J Cell Biol. 2011;194:825-39 pubmed publisher
    ..These data provide a novel mechanism by which Satb1, a direct downstream target of p63, contributes in epidermal morphogenesis via establishing tissue-specific chromatin organization and gene expression in epidermal progenitor cells. ..
  36. Yang Y, Yamada T, Hill K, Hemberg M, Reddy N, Cho H, et al. Chromatin remodeling inactivates activity genes and regulates neural coding. Science. 2016;353:300-305 pubmed publisher
    ..from synchronously developing granule neurons (Sync-TRAP) showed that conditional knockout of the core NuRD subunit Chd4 impairs inactivation of activity-dependent genes when neurons undergo dendrite pruning...
  37. Sun F, Yang Q, Weng W, Zhang Y, Yu Y, Hong A, et al. Chd4 and associated proteins function as corepressors of Sox9 expression during BMP-2-induced chondrogenesis. J Bone Miner Res. 2013;28:1950-61 pubmed publisher
    ..pathways analysis (IPA) revealed a protein-protein network with chromodomain-helicase-DNA-binding protein 4 (Chd4) in the center...
  38. Siatecka M, Xue L, Bieker J. Sumoylation of EKLF promotes transcriptional repression and is involved in inhibition of megakaryopoiesis. Mol Cell Biol. 2007;27:8547-60 pubmed
    ..These studies demonstrate a novel mechanism by which transcription factor sumoylation can alter protein-protein interactions and bipotential lineage decisions. ..
  39. McDonel P, Demmers J, Tan D, Watt F, Hendrich B. Sin3a is essential for the genome integrity and viability of pluripotent cells. Dev Biol. 2012;363:62-73 pubmed publisher
    ..These results indicate that Sin3a protects the genomic integrity of pluripotent embryonic cells and governs their unusual cell cycle. ..
  40. Chudnovsky Y, Kim D, Zheng S, Whyte W, Bansal M, Bray M, et al. ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state. Cell Rep. 2014;6:313-24 pubmed publisher
    ..ZFHX4 interacts with CHD4, a core member of the nucleosome remodeling and deacetylase (NuRD) complex...
  41. Denner D, Rauchman M. Mi-2/NuRD is required in renal progenitor cells during embryonic kidney development. Dev Biol. 2013;375:105-16 pubmed publisher
    ..We also demonstrated that Sall1 and Mi2? exhibited a strong in vivo genetic interaction in the developing kidney. Together these findings indicate that Sall1 and NuRD act cooperatively to maintain CM progenitor cells. ..
  42. Loebel D, O Rourke M, Steiner K, Banyer J, Tam P. Isolation of differentially expressed genes from wild-type and Twist mutant mouse limb buds. Genesis. 2002;33:103-13 pubmed