Skip to main content
SpringerLink
Log in

The NuRD architecture

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

The nucleosome remodeling and deacetylase (NuRD) complex regulates chromatin organization, gene transcription, genomic stability and developmental signaling. NuRD has a unique dual enzymatic activity, containing an ATPase and a histone deacetylase among its six core subunits. Recent studies indicate that NuRD composition and the interplay between subunits may dictate the diverse functions of the complex. In this review, we examine the structures and biological roles of the NuRD subunits and discuss new avenues of research to advance our understanding of the NuRD-mediated signaling network.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL (1998) Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex. Nature 395:917–921

    PubMed  CAS  Google Scholar 

  2. Wade PA, Jones PL, Vermaak D, Wolffe AP (1998) A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates with an associated Snf2 superfamily ATPase. Curr Biol 8:843–846

    PubMed  CAS  Google Scholar 

  3. Xue Y, Wong J, Moreno GT, Young MK, Cote J, Wang W (1998) NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol Cell 2:851–861

    PubMed  CAS  Google Scholar 

  4. Zhang Y, LeRoy G, Seelig HP, Lane WS, Reinberg D (1998) The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell 95:279–289

    PubMed  CAS  Google Scholar 

  5. Denslow SA, Wade PA (2007) The human Mi-2/NuRD complex and gene regulation. Oncogene 26:5433–5438

    PubMed  CAS  Google Scholar 

  6. Wang HB, Zhang Y (2001) Mi2, an auto-antigen for dermatomyositis, is an ATP-dependent nucleosome remodeling factor. Nucleic Acids Res 29:2517–2521

    PubMed  CAS  Google Scholar 

  7. Lai AY, Wade PA (2011) Cancer biology and NuRD: a multifaceted chromatin remodelling complex. Nat Rev Cancer 11:588–596

    PubMed  CAS  Google Scholar 

  8. Bowen NJ, Fujita N, Kajita M, Wade PA (2004) Mi-2/NuRD: multiple complexes for many purposes. Biochim Biophys Acta 1677:52–57

    PubMed  CAS  Google Scholar 

  9. Pegoraro G, Misteli T (2009) The central role of chromatin maintenance in aging. Aging (Albany NY) 1:1017–1022

    CAS  Google Scholar 

  10. Ge Q, Nilasena DS, O’Brien CA, Frank MB, Targoff IN (1995) Molecular analysis of a major antigenic region of the 240-kD protein of Mi-2 autoantigen. J Clin Invest 96:1730–1737

    PubMed  CAS  Google Scholar 

  11. Seelig HP, Moosbrugger I, Ehrfeld H, Fink T, Renz M, Genth E (1995) The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation. Arthritis Rheum 38:1389–1399

    PubMed  CAS  Google Scholar 

  12. Musselman CA, Mansfield RE, Garske AL, Davrazou F, Kwan AH, Oliver SS, O’Leary H, Denu JM, Mackay JP, Kutateladze TG (2009) Binding of the CHD4 PHD2 finger to histone H3 is modulated by covalent modifications. Biochem J 423:179–187

    PubMed  CAS  Google Scholar 

  13. Mansfield RE, Musselman CA, Kwan AH, Oliver SS, Garske AL, Davrazou F, Denu JM, Kutateladze TG, Mackay JP (2011) Plant homeodomain (PHD) fingers of CHD4 are histone H3-binding modules with preference for unmodified H3K4 and methylated H3K9. J Biol Chem 286:11779–11791

    PubMed  CAS  Google Scholar 

  14. Bouazoune K, Mitterweger A, Langst G, Imhof A, Akhtar A, Becker PB, Brehm A (2002) The dMi-2 chromodomains are DNA binding modules important for ATP-dependent nucleosome mobilization. EMBO J 21:2430–2440

    PubMed  CAS  Google Scholar 

  15. Hall JA, Georgel PT (2007) CHD proteins: a diverse family with strong ties. Biochem Cell Biol 85:463–476

    PubMed  CAS  Google Scholar 

  16. Musselman CA, Ramirez J, Sims JK, Mansfield RE, Oliver SS, Denu JM, Mackay JP, Wade PA, Hagman J, Kutateladze TG (2012) Bivalent recognition of nucleosomes by the tandem PHD fingers of the CHD4 ATPase is required for CHD4-mediated repression. Proc Natl Acad Sci USA 109:787–792

    PubMed  CAS  Google Scholar 

  17. Watson AA, Mahajan P, Mertens HD, Deery MJ, Zhang W, Pham P, Du X, Bartke T, Zhang W, Edlich C, Berridge G, Chen Y, Burgess-Brown NA, Kouzarides T, Wiechens N, Owen-Hughes T, Svergun DI, Gileadi O, Laue ED (2012) The PHD and chromo domains regulate the ATPase activity of the human chromatin remodeler CHD4. J Mol Biol 422:3–17

    PubMed  CAS  Google Scholar 

  18. Morra R, Lee BM, Shaw H, Tuma R, Mancini EJ (2012) Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4. FEBS Lett 586:2513–2521

    PubMed  CAS  Google Scholar 

  19. Kwan AHY, Gell DA, Verger A, Grossley M, Matthews JM, Mackay JP (2003) Engineering a protein scaffold from a PHD finger. Structure 11:803–813

    PubMed  CAS  Google Scholar 

  20. Blus BJ, Wiggins K, Khorasanizadeh S (2011) Epigenetic virtues of chromodomains. Crit Rev Biochem Mol Biol 46:507–526

    PubMed  CAS  Google Scholar 

  21. Ramirez J, Dege C, Kutateladze TG, Hagman J (2012). MBD2 and multiple domains of CHD4 are required for transcriptional repression by Mi-2/NuRD complexes. Mol Cell Biol

  22. Hauk G, McKnight JN, Nodelman IM, Bowman GD (2010) The chromodomains of the Chd1 chromatin remodeler regulate DNA access to the ATPase motor. Mol Cell 39:711–723

    PubMed  CAS  Google Scholar 

  23. Kehle J, Beuchle D, Treuheit S, Christen B, Kennison JA, Bienz M, Muller J (1998) dMi-2, a hunchback-interacting protein that functions in polycomb repression. Science 282:1897–1900

    PubMed  CAS  Google Scholar 

  24. Murawsky CM, Brehm A, Badenhorst P, Lowe N, Becker PB, Travers AA (2001) Tramtrack69 interacts with the dMi-2 subunit of the Drosophila NuRD chromatin remodelling complex. EMBO Rep 2:1089–1094

    PubMed  CAS  Google Scholar 

  25. Shimono Y, Murakami H, Kawai K, Wade PA, Shimokata K, Takahashi M (2003) Mi-2 beta associates with BRG1 and RET finger protein at the distinct regions with transcriptional activating and repressing abilities. J Biol Chem 278:51638–51645

    PubMed  CAS  Google Scholar 

  26. Srinivasan R, Mager GM, Ward RM, Mayer J, Svaren J (2006) NAB2 represses transcription by interacting with the CHD4 subunit of the nucleosome remodeling and deacetylase (NuRD) complex. J Biol Chem 281:15129–15137

    PubMed  CAS  Google Scholar 

  27. Schultz DC, Friedman JR, Rauscher FJ 3rd (2001) Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform of the Mi-2alpha subunit of NuRD. Genes Dev 15:428–443

    PubMed  CAS  Google Scholar 

  28. Brehm A, Nielsen SJ, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T (1999) The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth. EMBO J 18:2449–2458

    PubMed  CAS  Google Scholar 

  29. Johnson DR, Lovett JM, Hirsch M, Xia F, Chen JD (2004) NuRD complex component Mi-2beta binds to and represses RORgamma-mediated transcriptional activation. Biochem Biophys Res Commun 318:714–718

    PubMed  CAS  Google Scholar 

  30. Lemos TA, Passos DO, Nery FC, Kobarg J (2003) Characterization of a new family of proteins that interact with the C-terminal region of the chromatin-remodeling factor CHD-3. FEBS Lett 533:14–20

    PubMed  CAS  Google Scholar 

  31. Kim J, Sif S, Jones B, Jackson A, Koipally J, Heller E, Winandy S, Viel A, Sawyer A, Ikeda T, Kingston R, Georgopoulos K (1999) Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes. Immunity 10:345–355

    PubMed  CAS  Google Scholar 

  32. Taunton J, Hassig CA, Schreiber SL (1996) A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272:408–411

    PubMed  CAS  Google Scholar 

  33. Yang XJ, Seto E (2008) The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat Rev Mol Cell Biol 9:206–218

    PubMed  CAS  Google Scholar 

  34. Zhang Y, Sun ZW, Iratni R, Erdjument-Bromage H, Tempst P, Hampsey M, Reinberg D (1998) SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex. Mol Cell 1:1021–1031

    PubMed  CAS  Google Scholar 

  35. You A, Tong JK, Grozinger CM, Schreiber SL (2001) CoREST is an integral component of the CoREST- human histone deacetylase complex. Proc Natl Acad Sci USA 98:1454–1458

    PubMed  CAS  Google Scholar 

  36. Ordentlich P, Downes M, Xie W, Genin A, Spinner NB, Evans RM (1999) Unique forms of human and mouse nuclear receptor corepressor SMRT. Proc Natl Acad Sci USA 96:2639–2644

    PubMed  CAS  Google Scholar 

  37. Liang J, Wan M, Zhang Y, Gu P, Xin H, Jung SY, Qin J, Wong J, Cooney AJ, Liu D, Songyang Z (2008) Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells. Nat Cell Biol 10:731–739

    PubMed  CAS  Google Scholar 

  38. Segre CV, Chiocca S (2011) Regulating the regulators: the post-translational code of class I HDAC1 and HDAC2. J Biomed Biotechnol 2011:690848

    PubMed  Google Scholar 

  39. Thiagalingam S, Cheng KH, Lee HJ, Mineva N, Thiagalingam A, Ponte JF (2003) Histone deacetylases: unique players in shaping the epigenetic histone code. Ann N Y Acad Sci 983:84–100

    PubMed  CAS  Google Scholar 

  40. Bressi JC, Jennings AJ, Skene R, Wu Y, Melkus R, De Jong R, O’Connell S, Grimshaw CE, Navre M, Gangloff AR (2010) Exploration of the HDAC2 foot pocket: synthesis and SAR of substituted N-(2-aminophenyl)benzamides. Bioorg Med Chem Lett 20:3142–3145

    PubMed  CAS  Google Scholar 

  41. Finnin MS, Donigian JR, Cohen A, Richon VM, Rifkind RA, Marks PA, Breslow R, Pavletich NP (1999) Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature 401:188–193

    PubMed  CAS  Google Scholar 

  42. Wade PA, Gegonne A, Jones PL, Ballestar E, Aubry F, Wolffe AP (1999) Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. Nat Genet 23:62–66

    PubMed  CAS  Google Scholar 

  43. Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (1999) Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev 13:1924–1935

    PubMed  CAS  Google Scholar 

  44. Le Guezennec X, Vermeulen M, Brinkman AB, Hoeijmakers WA, Cohen A, Lasonder E, Stunnenberg HG (2006) MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties. Mol Cell Biol 26:843–851

    PubMed  Google Scholar 

  45. Hendrich B, Bird A (1998) Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol 18:6538–6547

    PubMed  CAS  Google Scholar 

  46. Hendrich B, Tweedie S (2003) The methyl-CpG binding domain and the evolving role of DNA methylation in animals. Trends Genet 19:269–277

    PubMed  CAS  Google Scholar 

  47. Hashimoto H, Liu Y, Upadhyay AK, Chang Y, Howerton SB, Vertino PM, Zhang X, Cheng X (2012) Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation. Nucleic Acids Res 40:4841–4849

    PubMed  CAS  Google Scholar 

  48. Saito M, Ishikawa F (2002) The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2. J Biol Chem 277:35434–35439

    PubMed  CAS  Google Scholar 

  49. Fraga MF, Ballestar E, Montoya G, Taysavang P, Wade PA, Esteller M (2003) The affinity of different MBD proteins for a specific methylated locus depends on their intrinsic binding properties. Nucleic Acids Res 31:1765–1774

    PubMed  CAS  Google Scholar 

  50. Marhold J, Brehm A, Kramer K (2004) The Drosophila methyl-DNA binding protein MBD2/3 interacts with the NuRD complex via p55 and MI-2. BMC Mol Biol 5:20

    PubMed  Google Scholar 

  51. Brackertz M, Gong Z, Leers J, Renkawitz R (2006) p66alpha and p66beta of the Mi-2/NuRD complex mediate MBD2 and histone interaction. Nucleic Acids Res 34:397–406

    PubMed  CAS  Google Scholar 

  52. Gnanapragasam MN, Scarsdale JN, Amaya ML, Webb HD, Desai MA, Walavalkar NM, Wang SZ, Zu Zhu S, Ginder GD, Williams DC Jr (2011) p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2–NuRD complex. Proc Natl Acad Sci USA 108:7487–7492

    PubMed  CAS  Google Scholar 

  53. Scarsdale JN, Webb HD, Ginder GD, Williams DC Jr (2011) Solution structure and dynamic analysis of chicken MBD2 methyl binding domain bound to a target-methylated DNA sequence. Nucleic Acids Res 39:6741–6752

    PubMed  CAS  Google Scholar 

  54. Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A (1999) MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nat Genet 23:58–61

    PubMed  CAS  Google Scholar 

  55. Sekimata M, Takahashi A, Murakami-Sekimata A, Homma Y (2001) Involvement of a novel zinc finger protein, MIZF, in transcriptional repression by interacting with a methyl-CpG-binding protein, MBD2. J Biol Chem 276:42632–42638

    PubMed  CAS  Google Scholar 

  56. Luo SW, Zhang C, Zhang B, Kim CH, Qiu YZ, Du QS, Mei L, Xiong WC (2009) Regulation of heterochromatin remodelling and myogenin expression during muscle differentiation by FAK interaction with MBD2. EMBO J 28:2568–2582

    PubMed  CAS  Google Scholar 

  57. Tatematsu KI, Yamazaki T, Ishikawa F (2000) MBD2–MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase. Genes Cells 5:677–688

    PubMed  CAS  Google Scholar 

  58. Hendrich B, Guy J, Ramsahoye B, Wilson VA, Bird A (2001) Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development. Genes Dev 15:710–723

    PubMed  CAS  Google Scholar 

  59. Qian YW, Wang YC, Hollingsworth RE Jr, Jones D, Ling N, Lee EY (1993) A retinoblastoma-binding protein related to a negative regulator of Ras in yeast. Nature 364:648–652

    PubMed  CAS  Google Scholar 

  60. Murzina NV, Pei XY, Zhang W, Sparkes M, Vicente-Garcia J, Pratap JV, McLaughlin SH, Ben-Shahar TR, Verreault A, Luisi BF, Laue ED (2008) Structural basis for the recognition of histone H4 by the histone-chaperone RbAp46. Structure 16:1077–1085

    PubMed  CAS  Google Scholar 

  61. Lejon S, Thong SY, Murthy A, AlQarni S, Murzina NV, Blobel GA, Laue ED, Mackay JP (2011) Insights into association of the NuRD complex with FOG-1 from the crystal structure of an RbAp48.FOG-1 complex. J Biol Chem 286:1196–1203

    PubMed  CAS  Google Scholar 

  62. Hong W, Nakazawa M, Chen YY, Kori R, Vakoc CR, Rakowski C, Blobel GA (2005) FOG-1 recruits the NuRD repressor complex to mediate transcriptional repression by GATA-1. EMBO J 24:2367–2378

    PubMed  CAS  Google Scholar 

  63. Yarden RI, Brody LC (1999) BRCA1 interacts with components of the histone deacetylase complex. Proc Natl Acad Sci USA 96:4983–4988

    PubMed  CAS  Google Scholar 

  64. Toh Y, Pencil SD, Nicolson GL (1994) A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses. J Biol Chem 269:22958–22963

    PubMed  CAS  Google Scholar 

  65. Armache KJ, Garlick JD, Canzio D, Narlikar GJ, Kingston RE (2011) Structural basis of silencing: Sir3 BAH domain in complex with a nucleosome at 3.0 A resolution. Science 334:977–982

    PubMed  CAS  Google Scholar 

  66. Horton JR, Elgar SJ, Khan SI, Zhang X, Wade PA, Cheng X (2007) Structure of the SANT domain from the Xenopus chromatin remodeling factor ISWI. Proteins 67:1198–1202

    PubMed  CAS  Google Scholar 

  67. Liew CK, Simpson RJ, Kwan AH, Crofts LA, Loughlin FE, Matthews JM, Crossley M, Mackay JP (2005) Zinc fingers as protein recognition motifs: structural basis for the GATA-1/friend of GATA interaction. Proc Natl Acad Sci USA 102:583–588

    PubMed  CAS  Google Scholar 

  68. Fujita N, Jaye DL, Geigerman C, Akyildiz A, Mooney MR, Boss JM, Wade PA (2004) MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation. Cell 119:75–86

    PubMed  CAS  Google Scholar 

  69. Cismasiu VB, Adamo K, Gecewicz J, Duque J, Lin Q, Avram D (2005) BCL11B functionally associates with the NuRD complex in T lymphocytes to repress targeted promoter. Oncogene 24:6753–6764

    PubMed  CAS  Google Scholar 

  70. Talukder AH, Mishra SK, Mandal M, Balasenthil S, Mehta S, Sahin AA, Barnes CJ, Kumar R (2003) MTA1 interacts with MAT1, a cyclin-dependent kinase-activating kinase complex ring finger factor, and regulates estrogen receptor transactivation functions. J Biol Chem 278:11676–11685

    PubMed  CAS  Google Scholar 

  71. Talukder AH, Gururaj A, Mishra SK, Vadlamudi RK, Kumar R (2004) Metastasis-associated protein 1 interacts with NRIF3, an estrogen-inducible nuclear receptor coregulator. Mol Cell Biol 24:6581–6591

    PubMed  CAS  Google Scholar 

  72. Mishra SK, Mazumdar A, Vadlamudi RK, Li F, Wang RA, Yu W, Jordan VC, Santen RJ, Kumar R (2003) MICoA, a novel metastasis-associated protein 1 (MTA1) interacting protein coactivator, regulates estrogen receptor-alpha transactivation functions. J Biol Chem 278:19209–19219

    PubMed  CAS  Google Scholar 

  73. Singh RR, Barnes CJ, Talukder AH, Fuqua SA, Kumar R (2005) Negative regulation of estrogen receptor alpha transactivation functions by LIM domain only 4 protein. Cancer Res 65:10594–10601

    PubMed  CAS  Google Scholar 

  74. Mazumdar A, Wang RA, Mishra SK, Adam L, Bagheri-Yarmand R, Mandal M, Vadlamudi RK, Kumar R (2001) Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Nat Cell Biol 3:30–37

    PubMed  CAS  Google Scholar 

  75. Feng Q, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Zhang Y (2002) Identification and functional characterization of the p66/p68 components of the MeCP1 complex. Mol Cell Biol 22:536–546

    PubMed  CAS  Google Scholar 

  76. Gong Z, Brackertz M, Renkawitz R (2006) SUMO modification enhances p66-mediated transcriptional repression of the Mi-2/NuRD complex. Mol Cell Biol 26:4519–4528

    PubMed  CAS  Google Scholar 

  77. Tyler JK, Kadonaga JT (1999) The “dark side” of chromatin remodeling: repressive effects on transcription. Cell 99:443–446

    PubMed  CAS  Google Scholar 

  78. Fujita N, Jaye DL, Kajita M, Geigerman C, Moreno CS, Wade PA (2003) MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell 113:207–219

    PubMed  CAS  Google Scholar 

  79. Gao Z, Huang Z, Olivey HE, Gurbuxani S, Crispino JD, Svensson EC (2010) FOG-1-mediated recruitment of NuRD is required for cell lineage re-enforcement during haematopoiesis. EMBO J 29:457–468

    PubMed  CAS  Google Scholar 

  80. Gao H, Lukin K, Ramirez J, Fields S, Lopez D, Hagman J (2009) Opposing effects of SWI/SNF and Mi-2/NuRD chromatin remodeling complexes on epigenetic reprogramming by EBF and Pax5. Proc Natl Acad Sci USA 106:11258–11263

    PubMed  CAS  Google Scholar 

  81. Cismasiu VB, Paskaleva E, Suman Daya S, Canki M, Duus K, Avram D (2008) BCL11B is a general transcriptional repressor of the HIV-1 long terminal repeat in T lymphocytes through recruitment of the NuRD complex. Virology 380:173–181

    PubMed  CAS  Google Scholar 

  82. Nishioka K, Chuikov S, Sarma K, Erdjument-Bromage H, Allis CD, Tempst P, Reinberg D (2002) Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev 16:479–489

    PubMed  CAS  Google Scholar 

  83. Zegerman P, Canas B, Pappin D, Kouzarides T (2002) Histone H3 lysine 4 methylation disrupts binding of nucleosome remodeling and deacetylase (NuRD) repressor complex. J Biol Chem 277:11621–11624

    PubMed  CAS  Google Scholar 

  84. Williams CJ, Naito T, Arco PG, Seavitt JR, Cashman SM, De Souza B, Qi X, Keables P, Von Andrian UH, Georgopoulos K (2004) The chromatin remodeler Mi-2beta is required for CD4 expression and T cell development. Immunity 20:719–733

    PubMed  CAS  Google Scholar 

  85. Yoshida T, Hazan I, Zhang J, Ng SY, Naito T, Snippert HJ, Heller EJ, Qi X, Lawton LN, Williams CJ, Georgopoulos K (2008) The role of the chromatin remodeler Mi-2beta in hematopoietic stem cell self-renewal and multilineage differentiation. Genes Dev 22:1174–1189

    PubMed  CAS  Google Scholar 

  86. Kaji K, Caballero IM, MacLeod R, Nichols J, Wilson VA, Hendrich B (2006) The NuRD component Mbd3 is required for pluripotency of embryonic stem cells. Nat Cell Biol 8:285–292

    PubMed  CAS  Google Scholar 

  87. Reynolds N, Latos P, Hynes-Allen A, Loos R, Leaford D, O’Shaughnessy A, Mosaku O, Signolet J, Brennecke P, Kalkan T, Costello I, Humphreys P, Mansfield W, Nakagawa K, Strouboulis J, Behrens A, Bertone P, Hendrich B (2012) NuRD suppresses pluripotency gene expression to promote transcriptional heterogeneity and lineage commitment. Cell Stem Cell 10:583–594

    PubMed  CAS  Google Scholar 

  88. Whyte WA, Bilodeau S, Orlando DA, Hoke HA, Frampton GM, Foster CT, Cowley SM, Young RA (2012) Enhancer decommissioning by LSD1 during embryonic stem cell differentiation. Nature 482:221–225

    PubMed  CAS  Google Scholar 

  89. Yildirim O, Li R, Hung JH, Chen PB, Dong X, Ee LS, Weng Z, Rando OJ, Fazzio TG (2012) Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells. Cell 147:1498–1510

    Google Scholar 

  90. Covault J, Chalkley R (1980) The identification of distinct populations of acetylated histone. J Biol Chem 255:9110–9116

    PubMed  CAS  Google Scholar 

  91. Nelson D, Covault J, Chalkley R (1980) Segregation of rapidly acetylated histones into a chromatin fraction released from intact nuclei by the action of micrococcal nuclease. Nucleic Acids Res 8:1745–1763

    PubMed  CAS  Google Scholar 

  92. Hu G, Wade PA (2012) NuRD and pluripotency: a complex balancing act. Cell Stem Cell 10:497–503

    PubMed  CAS  Google Scholar 

  93. Smeenk G, Wiegant WW, Vrolijk H, Solari AP, Pastink A, van Attikum H (2010) The NuRD chromatin-remodeling complex regulates signaling and repair of DNA damage. J Cell Biol 190:741–749

    PubMed  CAS  Google Scholar 

  94. Li DQ, Ohshiro K, Reddy SD, Pakala SB, Lee MH, Zhang Y, Rayala SK, Kumar R (2009) E3 ubiquitin ligase COP1 regulates the stability and functions of MTA1. Proc Natl Acad Sci USA 106:17493–17498

    PubMed  CAS  Google Scholar 

  95. Polo SE, Kaidi A, Baskcomb L, Galanty Y, Jackson SP (2010) Regulation of DNA-damage responses and cell-cycle progression by the chromatin remodelling factor CHD4. EMBO J 29:3130–3139

    PubMed  CAS  Google Scholar 

  96. Chou DM, Adamson B, Dephoure NE, Tan X, Nottke AC, Hurov KE, Gygi SP, Colaiacovo MP, Elledge SJ (2010) A chromatin localization screen reveals poly (ADP ribose)-regulated recruitment of the repressive polycomb and NuRD complexes to sites of DNA damage. Proc Natl Acad Sci USA 107:18475–18480

    PubMed  CAS  Google Scholar 

  97. Larsen DH, Poinsignon C, Gudjonsson T, Dinant C, Payne MR, Hari FJ, Rendtlew Danielsen JM, Menard P, Sand JC, Stucki M, Lukas C, Bartek J, Andersen JS, Lukas J (2010) The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage. J Cell Biol 190:731–740

    PubMed  CAS  Google Scholar 

  98. Helbling Chadwick L, Chadwick BP, Jaye DL, Wade PA (2009) The Mi-2/NuRD complex associates with pericentromeric heterochromatin during S phase in rapidly proliferating lymphoid cells. Chromosoma 118:445–457

    PubMed  Google Scholar 

  99. Sims JK, Wade PA (2011) Mi-2/NuRD complex function is required for normal S phase progression and assembly of pericentric heterochromatin. Mol Biol Cell 22:3094–3102

    PubMed  CAS  Google Scholar 

  100. Fasulo B, Deuring R, Murawska M, Gause M, Dorighi KM, Schaaf CA, Dorsett D, Brehm A, Tamkun JW (2012) The Drosophila MI-2 chromatin-remodeling factor regulates higher-order chromatin structure and cohesin dynamics in vivo. PLoS Genet 8:e1002878

    PubMed  CAS  Google Scholar 

  101. Casciola-Rosen L, Mammen AL (2012) Myositis autoantibodies. Curr Opin Rheumatol 24:602–608

    PubMed  CAS  Google Scholar 

  102. Casciola-Rosen L, Nagaraju K, Plotz P, Wang K, Levine S, Gabrielson E, Corse A, Rosen A (2005) Enhanced autoantigen expression in regenerating muscle cells in idiopathic inflammatory myopathy. J Exp Med 201:591–601

    PubMed  CAS  Google Scholar 

  103. Mammen AL, Casciola-Rosen LA, Hall JC, Christopher-Stine L, Corse AM, Rosen A (2009) Expression of the dermatomyositis autoantigen Mi-2 in regenerating muscle. Arthritis Rheum 60:3784–3793

    PubMed  CAS  Google Scholar 

  104. Pegoraro G, Kubben N, Wickert U, Gohler H, Hoffmann K, Misteli T (2009) Ageing-related chromatin defects through loss of the NURD complex. Nat Cell Biol 11:1261–1267

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors apologize to our many colleagues whose work could not be cited here due to space constraints. This work was supported by the NIH grant, GM096863 to T.G.K. This work was supported, in part, by the Intramural Research Program of the US National Institute of Environmental Health Sciences, NIH (Project Number Z01ES101965 to P.A.W.). H.F.A. is supported by the Neuroscience Graduate training grant, T32HD041697.

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, 80045, USA

    Hillary F. Allen & Tatiana G. Kutateladze

  2. Neuroscience Program, University of Colorado School of Medicine, Aurora, CO, 80045, USA

    Hillary F. Allen & Tatiana G. Kutateladze

  3. Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA

    Paul A. Wade

Authors
  1. Hillary F. Allen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul A. Wade
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tatiana G. Kutateladze
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tatiana G. Kutateladze.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Allen, H.F., Wade, P.A. & Kutateladze, T.G. The NuRD architecture. Cell. Mol. Life Sci. 70, 3513–3524 (2013). https://doi.org/10.1007/s00018-012-1256-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-012-1256-2

Keywords

Search

Navigation