The spatial dynamics of tissue-specific promoters during C. elegans development.
To understand whether the spatial organization of the genome reflects the cell's differentiated state, we examined whether genes assume specific subnuclear positions during Caenorhabditis elegans development. Monitoring the radial position of developmentally controlled promoters in embryos and larval tissues, we found that small integrated arrays bearing three different tissue-specific promoters have no preferential position in nuclei of undifferentiated embryos. However, in differentiated cells, they shifted stably toward the nuclear lumen when activated, or to the nuclear envelope when silent. In contrast, large integrated arrays bearing the same promoters became heterochromatic and nuclear envelope-bound in embryos. Tissue-specific activation of promoters in these large arrays in larvae overrode the perinuclear anchorage. For transgenes that carry both active and inactive promoters, the inward shift of the active promoter was dominant. Finally, induction of master regulator HLH-1 prematurely induced internalization of a muscle-specific promoter array in embryos. Fluorescence in situ hybridization confirmed analogous results for the endogenous endoderm-determining gene pha-4. We propose that, in differentiated cells, subnuclear organization arises from the selective positioning of active and inactive developmentally regulated promoters. We characterize two forces that lead to tissue-specific subnuclear organization of the worm genome: large repeat-induced heterochromatin, which associates with the nuclear envelope like repressed genes in differentiated cells, and tissue-specific promoters that shift inward in a dominant fashion over silent promoters, when they are activated.
Meister
Peter
P
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Towbin
Benjamin D
BD
Pike
Brietta L
BL
Ponti
Aaron
A
Gasser
Susan M
SM
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D003094:Collagen / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006570:Heterochromatin / Q000235:genetics; D008957:Models, Genetic; D032342:Muscle Cells / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics; D019076:Transgenes / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D006570:Heterochromatin; C113277:Pha-4 protein, C elegans; D015534:Trans-Activators; C098282:rol-6 protein, C elegans; D003094:Collagen
Science. 2004 Feb 20;303(5661):1182-5
14976312
Nat Immunol. 2007 Apr;8(4):378-87
17334367
Genes Dev. 2006 Dec 15;20(24):3395-406
17142668
Science. 2004 Oct 22;306(5696):644-7
15499009
Dev Biol. 1996 Sep 15;178(2):289-303
8812130
Mol Biol Cell. 2000 Nov;11(11):3937-47
11071918
Nature. 2007 May 24;447(7143):413-7
17522674
Science. 2002 Apr 5;296(5565):158-62
11935030
Trends Cell Biol. 2001 Jun;11(6):250-7
11356361
Cell. 2004 Dec 29;119(7):955-67
15620354
Dev Biol. 1985 Jan;107(1):128-33
2578115
Dev Biol. 1977 Mar;56(1):110-56
838129
Curr Opin Genet Dev. 2009 Apr;19(2):180-6
19303765
Eur J Immunol. 2004 Dec;34(12):3604-13
15484194
Genetics. 1995 Nov;141(3):977-88
8582641
BMC Genet. 2006 Jun 07;7:36
16759392
Curr Opin Genet Dev. 2006 Oct;16(5):455-62
16920351
Science. 2005 May 20;308(5725):1164-7
15790806
Genetics. 2001 Mar;157(3):1217-26
11238406
Mol Cell. 2000 Sep;6(3):705-13
11030349
Yeast. 2008 Mar;25(3):235-9
18302313
J Cell Sci. 2006 Jan 1;119(Pt 1):132-40
16371653
Genes Dev. 2006 Jun 1;20(11):1447-57
16705039
Development. 1998 Jun;125(12):2171-80
9584117
J Cell Biol. 2001 Jul 9;154(1):33-48
11448988
Exp Cell Res. 2000 Mar 15;255(2):229-37
10694438
Nat Cell Biol. 2001 Jun;3(6):602-6
11389446
Nature. 2009 Jul 2;460(7251):49-52
19571877
Dev Cell. 2009 May;16(5):699-710
19460346
Nucleic Acids Res. 2005 Oct 27;33(18):e163
16254074
Curr Biol. 2006 Apr 18;16(8):825-31
16631592
Cell. 2004 Mar 5;116(5):683-98
15006351
Nat Genet. 2006 Sep;38(9):1005-14
16878134
Genes Dev. 1998 Jul 1;12(13):1947-52
9649499
J Cell Biol. 1996 Dec;135(6 Pt 2):1685-700
8991083
Annu Rev Genet. 2000;34:187-204
11092826
PLoS Genet. 2010 Jan 22;6(1):e1000830
20107519
Science. 2002 May 24;296(5572):1412-6
12029120
Mol Cell Biol. 2002 May;22(10):3437-49
11971975
Cell. 2007 Feb 23;128(4):735-45
17320510
Development. 1994 Oct;120(10):3019-31
7607089
Nat Methods. 2008 Aug;5(8):703-9
18587405
Annu Rev Genet. 2004;38:305-45
15568979
Development. 2005 Apr;132(8):1795-805
15772130
Genes Dev. 2004 Jun 15;18(12):1371-84
15198979
J Cell Sci. 2002 Jan 1;115(Pt 1):61-70
11801724
J Cell Biol. 1999 Jun 28;145(7):1341-54
10385516
Genetics. 1991 Dec;129(4):1061-72
1783292
Genes Dev. 2008 Feb 15;22(4):489-98
18281462
J Cell Biol. 2004 Sep 13;166(6):815-25
15364959
Genes Dev. 1999 Jan 1;13(1):112-24
9887104
Genes Dev. 2005 Mar 15;19(6):683-96
15741313
Trends Genet. 2009 Mar;25(3):129-36
19185382
Genes Dev. 2007 Dec 1;21(23):3027-43
18056419
J Cell Sci. 2001 Dec;114(Pt 24):4485-98
11792814
Methods Enzymol. 2004;375:345-65
14870677
Development. 2005 Apr;132(8):1843-54
15772128
Methods Enzymol. 2010;470:535-67
20946824
Development. 2007 Aug;134(16):2991-9
17634190
Nature. 1998 Nov 12;396(6707):168-73
9823896
Annu Rev Biochem. 2003;72:573-608
14527325
J Cell Sci. 2004 Sep 1;117(Pt 19):4603-14
15331668
J Cell Biol. 1992 Mar;116(5):1095-110
1740468
Cytometry A. 2004 Apr;58(2):157-66
15057969
J Cell Biol. 2002 Dec 9;159(5):753-63
12473685
Mol Endocrinol. 2006 Nov;20(11):2641-55
16873444
Nat Rev Genet. 2007 Jul;8(7):507-17
17549064