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Chromatin remodelling during development

Nature volume 463, pages 474484 (28 January 2010) | Download Citation

Abstract

New methods for the genome-wide analysis of chromatin are providing insight into its roles in development and their underlying mechanisms. Current studies indicate that chromatin is dynamic, with its structure and its histone modifications undergoing global changes during transitions in development and in response to extracellular cues. In addition to DNA methylation and histone modification, ATP-dependent enzymes that remodel chromatin are important controllers of chromatin structure and assembly, and are major contributors to the dynamic nature of chromatin. Evidence is emerging that these chromatin-remodelling enzymes have instructive and programmatic roles during development. Particularly intriguing are the findings that specialized assemblies of ATP-dependent remodellers are essential for establishing and maintaining pluripotent and multipotent states in cells.

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References

  1. 1.

    Chromatin structure: a repeating unit of histones and DNA. Science 184, 868–871 (1974).

  2. 2.

    & DNA methylation landscapes: provocative insights from epigenomics. Nature Rev. Genet. 9, 465–476 (2008).

  3. 3.

    et al. Linking covalent histone modifications to epigenetics: the rigidity and plasticity of the marks. Cold Spring Harb. Symp. Quant. Biol. 69, 161–169 (2004).

  4. 4.

    , , & Stimulation of GAL4 derivative binding to nucleosomal DNA by the yeast SWI/SNF complex. Science 265, 53–60 (1994).

  5. 5.

    & Genome-wide approaches to studying chromatin modifications. Nature Rev. Genet. 9, 179–191 (2008).

  6. 6.

    , & Understanding the words of chromatin regulation. Cell 136, 200–206 (2009).

  7. 7.

    & ATP-dependent chromatin remodeling in neural development. Curr. Opin. Neurobiol. 19, 120–126 (2009).

  8. 8.

    et al. The ISWI chromatin-remodeling protein is required for gene expression and the maintenance of higher order chromatin structure in vivo. Mol. Cell 5, 355–365 (2000).

  9. 9.

    & Chromatin remodelling beyond transcription: the INO80 and SWR1 complexes. Nature Rev. Mol. Cell Biol. 10, 373–384 (2009).

  10. 10.

    Sequential roles of Brg, the ATPase subunit of BAF chromatin remodeling complexes, in thymocyte development. Immunity 19, 169–182 (2003).

  11. 11.

    & The BRG1 transcriptional coregulator. Nucl. Recept. Signal. 6, e004 (2008).

  12. 12.

    et al. Endocardial Brg1 represses ADAMTS1 to maintain the microenvironment for myocardial morphogenesis. Dev. Cell 14, 298–311 (2008).

  13. 13.

    et al. Regulation of dendritic development by neuron-specific chromatin remodeling complexes. Neuron 56, 94–108 (2007).

  14. 14.

    et al. Rnf2 (Ring1b) deficiency causes gastrulation arrest and cell cycle inhibition. Proc. Natl Acad. Sci. USA 100, 2468–2473 (2003).

  15. 15.

    et al. Bmi1 regulates mitochondrial function and the DNA damage response pathway. Nature 459, 387–392 (2009).

  16. 16.

    et al. Chromatin remodelling factor Mll1 is essential for neurogenesis from postnatal neural stem cells. Nature 458, 529–533 (2009).

  17. 17.

    & Dosage-dependent modifiers of polycomb and antennapedia mutations in Drosophila. Proc. Natl Acad. Sci. USA 85, 8136–8140 (1988).

  18. 18.

    et al. The transcriptional coactivator SAYP is a trithorax group signature subunit of the PBAP chromatin remodeling complex. Mol. Cell. Biol. 28, 2920–2929 (2008).

  19. 19.

    et al. The Drosophila snr1 and brm proteins are related to yeast SWI/SNF proteins and are components of a large protein complex. Mol. Biol. Cell 6, 777–791 (1995).

  20. 20.

    et al. The Drosophila BRM complex facilitates global transcription by RNA polymerase II. EMBO J. 21, 5245–5254 (2002).

  21. 21.

    et al. Stabilization of chromatin structure by PRC1, a Polycomb complex. Cell 98, 37–46 (1999).

  22. 22.

    , & How many remodelers does it take to make a brain? Diverse and cooperative roles of ATP-dependent chromatin-remodeling complexes in development. Biochem. Cell Biol. 85, 444–462 (2007).

  23. 23.

    et al. Diversity and specialization of mammalian SWI/SNF complexes. Genes Dev. 10, 2117–2130 (1996).

  24. 24.

    et al. An essential switch in subunit composition of a chromatin remodeling complex during neural development. Neuron 55, 201–215 (2007).

  25. 25.

    et al. Maternal BRG1 regulates zygotic genome activation in the mouse. Genes Dev. 20, 1744–1754 (2006).

  26. 26.

    et al. A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. Mol. Cell 6, 1287–1295 (2000).

  27. 27.

    et al. Altered control of cellular proliferation in the absence of mammalian brahma (SNF2α). EMBO J. 17, 6979–6991 (1998).

  28. 28.

    et al. BAF250B-associated SWI/SNF chromatin-remodeling complex is required to maintain undifferentiated mouse embryonic stem cells. Stem Cells 26, 1155–1165 (2008).

  29. 29.

    et al. An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency. Proc. Natl Acad. Sci. USA 106, 5181–5186 (2009).

  30. 30.

    , & SWI/SNF–Brg1 regulates self-renewal and occupies core pluripotency-related genes in embryonic stem cells. Stem Cells 27, 317–328 (2008).

  31. 31.

    et al. ES cell pluripotency and germ-layer formation require the SWI/SNF chromatin remodeling component BAF250a. Proc. Natl Acad. Sci. USA 105, 6656–6661 (2008).

  32. 32.

    et al. An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network. Proc. Natl Acad. Sci. USA 106, 5187–5191 (2009).

  33. 33.

    , , & Nuclear reprogramming of human somatic cells by Xenopus egg extract requires BRG1. Curr. Biol. 14, 1475–1480 (2004).

  34. 34.

    et al. The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression. EMBO Rep. 1, 500–506 (2000).

  35. 35.

    et al. Srg3, a mouse homolog of yeast SWI3, is essential for early embryogenesis and involved in brain development. Mol. Cell Biol. 21, 7787–7795 (2001).

  36. 36.

    et al. Smarcc1/Baf155 couples self-renewal gene repression with changes in chromatin structure in mouse embryonic stem cells. Stem Cells doi:10.1002/stem.223 (25 September 2009).

  37. 37.

    , , & Genome-wide analyses identify transcription factors required for proper morphogenesis of Drosophila sensory neuron dendrites. Genes Dev. 20, 820–835 (2006).

  38. 38.

    , , & MicroRNA-mediated switching of chromatin-remodelling complexes in neural development. Nature 460, 642–646 (2009).

  39. 39.

    et al. Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex. Genes Dev. 22, 2370–2384 (2008).

  40. 40.

    et al. Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature 432, 107–112 (2004).

  41. 41.

    et al. Baf60c is a nuclear Notch signaling component required for the establishment of left–right asymmetry. Proc. Natl Acad. Sci. USA 104, 846–851 (2007).

  42. 42.

    & Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature 459, 708–711 (2009). This study showed that BAF60C, together with two cardiogenic transcription factors (GATA4 and TBX5), is sufficient to direct heart formation in non-cardiogenic tissues in developing embyros, demonstrating that chromatin remodelling by specific BAF complexes can be both necessary and sufficient for specific fate induction.

  43. 43.

    et al. Polybromo protein BAF180 functions in mammalian cardiac chamber maturation. Genes Dev. 18, 3106–3116 (2004).

  44. 44.

    , , , & Coronary development is regulated by ATP-dependent SWI/SNF chromatin remodeling component BAF180. Dev. Biol. 319, 258–266 (2008).

  45. 45.

    , , & A lineage-specific transcriptional silencer regulates CD4 gene expression during T lymphocyte development. Cell 77, 917–929 (1994).

  46. 46.

    et al. Molecular basis of CD4 repression by the Swi/Snf-like BAF chromatin remodeling complex. Eur. J. Immunol. 39, 580–588 (2009).

  47. 47.

    et al. Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes. Nature 418, 195–199 (2002).

  48. 48.

    , & Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle- and developmentally regulated promoter. Cell 97, 299–311 (1999).

  49. 49.

    , , , & BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription. Nature 366, 170–174 (1993).

  50. 50.

    , & Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation. Nature Genet. 27, 187–190 (2001).

  51. 51.

    & Functional diversity of ISWI complexes. Biochem. Cell Biol. 82, 482–489 (2004).

  52. 52.

    et al. ISWI regulates higher-order chromatin structure and histone H1 assembly in vivo. PLoS Biol. 5, e232 (2007).

  53. 53.

    , , , & Drosophila ISWI regulates the association of histone H1 with interphase chromosomes in vivo. Genetics 182, 661–669 (2009).

  54. 54.

    & Stem cell self-renewal controlled by chromatin remodeling factors. Science 310, 1487–1489 (2005).

  55. 55.

    , , & Biological functions of the ISWI chromatin remodeling complex NURF. Genes Dev. 16, 3186–3198 (2002).

  56. 56.

    et al. Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells. PLoS Genet. 4, e1000241 (2008).

  57. 57.

    et al. CECR2, a protein involved in neurulation, forms a novel chromatin remodeling complex with SNF2L. Hum. Mol. Genet. 14, 513–524 (2005).

  58. 58.

    & The, ISWI ATPase Snf2h is required for early mouse development. Proc. Natl Acad. Sci. USA 100, 14097–14102 (2003).

  59. 59.

    Williams–Beuren syndrome: genes and mechanisms. Hum. Mol. Genet. 8, 1947–1954 (1999).

  60. 60.

    et al. Distinct function of 2 chromatin remodeling complexes that share a common subunit, Williams syndrome transcription factor (WSTF). Proc. Natl Acad. Sci. USA 106, 9280–9285 (2009).

  61. 61.

    & CHD proteins: a diverse family with strong ties. Biochem. Cell Biol. 85, 463–476 (2007).

  62. 62.

    et al. Double chromodomains cooperate to recognize the methylated histone H3 tail. Nature 438, 1181–1185 (2005).

  63. 63.

    et al. Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing. Mol. Cell 28, 665–676 (2007).

  64. 64.

    , , , & Investigations of CHD1 function in transcription and development of Drosophila melanogaster. Genetics 178, 583–587 (2008).

  65. 65.

    et al. CHD1 motor protein is required for deposition of histone variant H3.3 into chromatin in vivo. Science 317, 1087–1090 (2007). This was the first study to show the ability of CHD1 to incorporate H3.3 into paternal chromatin, rendering it competent for post-fertilization mitosis, possibly explaining the sterility of CHD1-deficient D. melanogaster.

  66. 66.

    & Transcription in the absence of histone H3.3. Curr. Biol. 19, 1221–1226 (2009).

  67. 67.

    et al. Chd1 regulates open chromatin and pluripotency of embryonic stem cells. Nature 460, 802–803 (2009).

  68. 68.

    , , , & The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell 95, 279–289 (1998).

  69. 69.

    , , & Mi-2/NuRD: multiple complexes for many purposes. Biochim. Biophys. Acta 1677, 52–57 (2004).

  70. 70.

    & The MeCP1 complex represses transcription through preferential binding, remodeling, and deacetylating methylated nucleosomes. Genes Dev. 15, 827–832 (2001).

  71. 71.

    & The human Mi-2/NuRD complex and gene regulation. Oncogene 26, 5433–5438 (2007).

  72. 72.

    , & Mbd3, a component of the NuRD co-repressor complex, is required for development of pluripotent cells. Development 134, 1123–1132 (2007).

  73. 73.

    et al. The NuRD component Mbd3 is required for pluripotency of embryonic stem cells. Nature Cell Biol. 8, 285–292 (2006).

  74. 74.

    et al. The chromatin remodeler Mi-2β is required for CD4 expression and T cell development. Immunity 20, 719–733 (2004).

  75. 75.

    et al. The role of the chromatin remodeler Mi-2β in hematopoietic stem cell self-renewal and multilineage differentiation. Genes Dev. 22, 1174–1189 (2008).

  76. 76.

    et al. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nature Genet. 36, 955–957 (2004).

  77. 77.

    et al. Loss of Chd7 function in gene-trapped reporter mice is embryonic lethal and associated with severe defects in multiple developing tissues. Mamm. Genome 18, 94–104 (2007).

  78. 78.

    et al. Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns. Genome Res. 19, 590–601 (2009).

  79. 79.

    , & Drosophila Kismet regulates histone H3 lysine 27 methylation and early elongation by RNA polymerase II. PLoS Genet. 4, e1000217 (2008).

  80. 80.

    & INO80 subfamily of chromatin remodeling complexes. Mutat. Res. 618, 18–29 (2007).

  81. 81.

    et al. ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex. Science 303, 343–348 (2004).

  82. 82.

    et al. Purification of a human SRCAP complex that remodels chromatin by incorporating the histone variant H2A.Z into nucleosomes. Biochemistry 45, 5671–5677 (2006).

  83. 83.

    , & The chromatin remodeling protein, SRCAP, is critical for deposition of the histone variant H2A.Z at promoters. J. Biol. Chem. 282, 26132–26139 (2007).

  84. 84.

    et al. H2AZ is enriched at Polycomb complex target genes in ES cells and is necessary for lineage commitment. Cell 135, 649–661 (2008).

  85. 85.

    , & Cellular functions of TIP60. Int. J. Biochem. Cell Biol. 38, 1496–1509 (2006).

  86. 86.

    et al. Disruption of Trrap causes early embryonic lethality and defects in cell cycle progression. Nature Genet. 29, 206–211 (2001).

  87. 87.

    , & An RNAi screen of chromatin proteins identifies Tip60−p400 as a regulator of embryonic stem cell identity. Cell 134, 162–174 (2008). This paper reports an RNAi screen of mouse ESCs for chromatin proteins that are crucial for pluripotency and self-renewal. Two major classes of remodeller, TIP60-p400 and BAF complexes, were found to be essential.

  88. 88.

    & Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132, 567–582 (2008).

  89. 89.

    , , , & Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nature Rev. Genet. 8, 104–115 (2007).

  90. 90.

    , , & Capturing chromosome conformation. Science 295, 1306–1311 (2002).

  91. 91.

    , & Chromatin remodelling in mammalian differentiation: lessons from ATP-dependent remodellers. Nature Rev. Genet. 7, 461–473 (2006).

  92. 92.

    , Kowenz-, & Cooperation between C/EBPα TBP/TFIIB and SWI/SNF recruiting domains is required for adipocyte differentiation. Genes Dev. 15, 3208–3216 (2001).

  93. 93.

    , & A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in β-globin expression and erythroid development. Genes Dev. 19, 2849–2861 (2005).

  94. 94.

    , , , & BRD7, a novel PBAF-specific SWI/SNF subunit, is required for target gene activation and repression in embryonic stem cells. J. Biol. Chem. 283, 32254–32263 (2008).

  95. 95.

    et al. Mutation of the SNF2 family member Chd2 affects mouse development and survival. J. Cell. Physiol. 209, 162–171 (2006).

  96. 96.

    et al. CHD5 is a tumor suppressor at human 1p36. Cell 128, 459–475 (2007).

  97. 97.

    et al. Definition and characterization of a region of 1p36.3 consistently deleted in neuroblastoma. Oncogene 24, 2684–2694 (2005).

  98. 98.

    et al. Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome. Hum. Mol. Genet. 18, 1909–1923 (2009).

  99. 99.

    , ,& In vivo association of CReMM/CHD9 with promoters in osteogenic cells. J. Cell. Physiol. 207, 374–378 (2006).

  100. 100.

    et al. NoRC — a novel member of mammalian ISWI-containing chromatin remodeling machines. EMBO J. 20, 4892–4900 (2001).

  101. 101.

    et al. Isolation of human NURF: a regulator of Engrailed gene expression. EMBO J. 22, 6089–6100 (2003).

  102. 102.

    & The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications. Clin. Exp. Metastasis 26, 215–227 (2009).

  103. 103.

    et al. Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev. Cell 10, 105–116 (2006).

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Acknowledgements

We thank A. Yoo, A. Shalizi and J. Ronan for comment and critique throughout the preparation of this article. L.H. is funded by the Agency for Science, Technology and Research (Singapore). G.R.C. is funded by grants from the National Institutes of Health and the Howard Hughes Medical Institute.

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  1. Stanford University Medical School, Room B211, Beckman Center, 279 Campus Drive, Stanford, California 94305, USA.

    • Lena Ho
    •  & Gerald R. Crabtree

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The authors declare no competing financial interests.

Reprints and permissions information is available at http://www.nature.com/reprints. Correspondence should be addressed to G.R.C. (crabtree@stanford.edu).

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