Abstract
All developmental processes in metazoans require the establishment of different genetic programs to generate functionally specialised cells. Differential gene expression is also the basis for the alterations in the developmental potential of differentiating cells. However, the molecular details concerning how this is achieved are still poorly understood. The haematopoietic system has for many years served as an excellent model system to study how developmental processes are regulated at the epigenetic level. In this article we will summarise recent results from others and from our own laboratory that have yielded profound insights into the general principles of how cell-fate decisions are regulated in the cell nucleus. We summarise (1) how the interplay of sequence-specific transcription factors and chromatin components is responsible for the cell type and cell stage-specific activation of specific genes and (2) how these findings impact on current concepts of epigenetic regulation of developmental processes.
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References
Belikov S, Holmqvist PH, Astrand C, Wrange O (2004) Nuclear factor 1 and octamer transcription factor 1 binding preset the chromatin structure of the mouse mammary tumor virus promoter for hormone induction. J Biol Chem 279:49857–49867
Bhende PM, Seaman WT, Delecluse HJ, Kenney SC (2004) The EBV lytic switch protein, Z, preferentially binds to and activates the methylated viral genome. Nat Genet 36:1099–1104
Bruniquel D, Schwartz RH (2003) Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process. Nat Immunol 4:235–240
Cirillo LA, Zaret KS (1999) An early developmental transcription factor complex that is more stable on nucleosome core particles than on free DNA. Mol Cell 4:961–969
DeKoter RP, Singh H (2000) Regulation of B lymphocyte and macrophage development by graded expression of PU.1. Science 288:1439–1441
Dillon N, Festenstein R (2002) Unravelling heterochromatin: competition between positive and negative factors regulates accessibility. Trends Genet 18:252–258
Enver T, Greaves M (1998) Loops, lineage, and leukemia. Cell 94:9–12
Gilbert N, Boyle S, Fiegler H, Woodfine K, Carter NP, Bickmore WA (2004) Chromatin architecture of the human genome: gene-rich domains are enriched in open chromatin fibers. Cell 118:555–566
Graf T (2002) Differentiation plasticity of hematopoietic cells. Blood 99:3089–3101
Hayashi K, Yamamoto M, Nojima T, Goitsuka R, Kitamura D (2003) Distinct signaling requirements for Dmu selection, IgH allelic exclusion, pre-B cell transition, and tumor suppression in B cell progenitors. Immunity 18:825–836
Heyworth C, Pearson S, May G, Enver T (2002) Transcription factor-mediated lineage switching reveals plasticity in primary committed progenitor cells. EMBO J 21:3770–3781
Huber MC, Graf T, Sippel AE, Bonifer C (1995) Dynamic changes in the chromatin of the chicken lysozyme gene domain during differentiation of multipotent progenitors to macrophages. DNA Cell Biol 14:397–402
Hutchins AS, Mullen AC, Lee HW, Sykes KJ, High FA, Hendrich BD, Bird AP, Reiner SL (2002) Gene silencing quantitatively controls the function of a developmental trans-activator. Mol Cell 10:81–91
Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33Suppl:245–254
Jägle U, Muller AM, Kohler H, Bonifer C (1997) Role of positive and negative cis-regulatory elements in the transcriptional activation of the lysozyme locus in developing macrophages of transgenic mice. J Biol Chem 272:5871–5879
Kirillov A, Kistler B, Mostoslavsky R, Cedar H, Wirth T, Bergman Y (1996) A role for nuclear NF-kappa B in B-cell-specific demethylation of the Igkappa locus. Nat Genet 13:435–441
Kontaraki J, Chen HH, Riggs A, Bonifer C (2000) Chromatin fine structure profiles for a developmentally regulated gene: reorganization of the lysozyme locus before trans-activator binding and gene expression. Genes Dev 14:2106–2122
Kulessa H, Frampton J, Graf T (1995) GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts. Genes Dev 9:1250–1262
Lefevre P, Melnik S, Wilson N, Riggs AD, Bonifer C (2003) Developmentally regulated recruitment of transcription factors and chromatin modification activities to chicken lysozyme cis-regulatory elements in vivo. Mol Cell Biol 23:4386–4400
Maier H, Ostraat R, Gao H, Fields S, Shinton SA, Medina KL, Ikawa T, Murre C, Singh H, Hardy RR, Hagman J (2004) Early Bcell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Nat Immunol 5:1069–1077
Maison C, Almouzni G (2004) HP1 and the dynamics of heterochromatin maintenance. Nat Rev Mol Cell Biol 5:296–304
Makar KW, Wilson CB (2004) DNA methylation is a nonredundant repressor of the Th2 effector program. J Immunol 173:4402–4406
Matsuo K, Silke J, Georgiev O, Marti P, Giovannini N, Rungger D (1998) An embryonic demethylation mechanism involving binding of transcription factors to replicating DNA. EMBO J 17:1446–1453
McIvor Z, Hein S, Fiegler H, Schroeder T, Stocking C, Just U, Cross M (2003) Transient expression of PU.1 commits multipotent progenitors to a myeloid fate whereas continued expression favors macrophage over granulocyte differentiation. Exp Hematol 31:39–47
Mikkola I, Heavey B, Horcher M, Busslinger M (2002) Reversion of B cell commitment upon loss of Pax5 expression. Science 297:110–113
Mullen AC, Hutchins AS, Villarino AV, Lee HW, High FA, Cereb N, Yang SY, Hua X, Reiner SL (2001) Cell cycle controlling the silencing and functioning of mammalian activators. Curr Biol 11:1695–1699
Nerlov C, Graf T (1998) PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors. Genes Dev 12:2403–2412
Nerlov C, Querfurth E, Kulessa H, Graf T (2000) GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription. Blood 95:2543–2551
Nutt SL, Urbanek P, Rolink A, Busslinger M (1997) Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus. Genes Dev 11:476–491
Nutt SL, Morrison AM, Dorfler P, Rolink A, Busslinger M (1998) Identification of BSAP (Pax-5) target genes in early B-cell development by loss-and gain-of-function experiments. EMBO J 17:2319–2333
Orkin SH (2000) Diversification of haematopoietic stem cells to specific lineages. Nat Rev Genet 1:57–64
Schmittwolf C, Kirchhof N, Jauch A, Durr M, Harder F, Zenke M, Muller AM (2005) In vivo haematopoietic activity is induced in neurosphere cells by chromatin-modifying agents. EMBO J 24:554–566
Tagoh H, Melnik S, Lefevre P, Chong S, Riggs AD, Bonifer C (2004a) Dynamic reorganization of chromatin structure and selective DNA demethylation prior to stable enhancer complex formation during differentiation of primary hematopoietic cells in vitro. Blood 103:2950–2955
Tagoh H, Schebesta A, Lefevre P, Wilson N, Hume D, Busslinger M, Bonifer C (2004b) Epigenetic silencing of the c-fms locus during B-lymphopoiesis occurs in discrete steps and is reversible. EMBO J 23:4275–4285
Thomassin H, Flavin M, Espinas ML, Grange T (2001) Glucocorticoid-induced DNA demethylation and gene memory during development. EMBO J 20:1974–1983
Weissman IL, Anderson DJ, Gage F (2001) Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol 17:387–403
Xie H, Ye M, Feng R, Graf T (2004) Stepwise reprogramming of B cells into macrophages. Cell 117:663–676
Yamada T, Abe M, Higashi T, Yamamoto H, Kihara-Negishi F, Sakurai T, Shirai T, Oikawa T (2001) Lineage switch induced by overexpression of Ets family transcription factor PU.1 in murine erythroleukemia cells. Blood 97:2300–2307
Zhang P, Zhang X, Iwama A, Yu C, Smith KA, Mueller BU, Narravula S, Torbett BE, Orkin SH, Tenen DG (2000) PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding. Blood 96:2641–2648
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© 2006 Springer-Verlag Berlin Heidelberg
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Bonifer, C., Lefevre, P., Tagoh, H. (2006). The Regulation of Chromatin and DNA-Methylation Patterns in Blood Cell Development. In: Doerfler, W., Böhm, P. (eds) DNA Methylation: Development, Genetic Disease and Cancer. Current Topics in Microbiology and Immunology, vol 310. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-31181-5_1
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DOI: https://doi.org/10.1007/3-540-31181-5_1
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