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Activation of Estrogen-Responsive Genes Does Not Require Their Nuclear Co-Localization


The spatial organization of the genome in the nucleus plays a role in the regulation of gene expression. Whether co-regulated genes are subject to coordinated repositioning to a shared nuclear space is a matter of considerable interest and debate. We investigated the nuclear organization of estrogen receptor alpha (ERα) target genes in human breast epithelial and cancer cell lines, before and after transcriptional activation induced with estradiol. We find that, contrary to another report, the ERα target genes TFF1 and GREB1 are distributed in the nucleoplasm with no particular relationship to each other. The nuclear separation between these genes, as well as between the ERα target genes PGR and CTSD, was unchanged by hormone addition and transcriptional activation with no evidence for co-localization between alleles. Similarly, while the volume occupied by the chromosomes increased, the relative nuclear position of the respective chromosome territories was unaffected by hormone addition. Our results demonstrate that estradiol-induced ERα target genes are not required to co-localize in the nucleus.


Vyšlo v časopise: Activation of Estrogen-Responsive Genes Does Not Require Their Nuclear Co-Localization. PLoS Genet 6(4): e32767. doi:10.1371/journal.pgen.1000922
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1000922

Souhrn

The spatial organization of the genome in the nucleus plays a role in the regulation of gene expression. Whether co-regulated genes are subject to coordinated repositioning to a shared nuclear space is a matter of considerable interest and debate. We investigated the nuclear organization of estrogen receptor alpha (ERα) target genes in human breast epithelial and cancer cell lines, before and after transcriptional activation induced with estradiol. We find that, contrary to another report, the ERα target genes TFF1 and GREB1 are distributed in the nucleoplasm with no particular relationship to each other. The nuclear separation between these genes, as well as between the ERα target genes PGR and CTSD, was unchanged by hormone addition and transcriptional activation with no evidence for co-localization between alleles. Similarly, while the volume occupied by the chromosomes increased, the relative nuclear position of the respective chromosome territories was unaffected by hormone addition. Our results demonstrate that estradiol-induced ERα target genes are not required to co-localize in the nucleus.


Zdroje

1. FraserP

BickmoreW

2007 Nuclear organization of the genome and the potential for gene regulation. Nature 447 413 417

2. FullwoodMJ

RuanY

2009 ChIP-based methods for the identification of long-range chromatin interactions. J Cell Biochem 107 30 39

3. SimonisM

KlousP

SplinterE

MoshkinY

WillemsenR

2006 Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C). Nat Genet 38 1348 1354

4. ApostolouE

ThanosD

2008 Virus Infection Induces NF-kappaB-dependent interchromosomal associations mediating monoallelic IFN-beta gene expression. Cell 134 85 96

5. BacherCP

GuggiariM

BrorsB

AuguiS

ClercP

2006 Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation. Nat Cell Biol 8 293 299

6. LomvardasS

BarneaG

PisapiaDJ

MendelsohnM

KirklandJ

2006 Interchromosomal interactions and olfactory receptor choice. Cell 126 403 413

7. OsborneCS

ChakalovaL

BrownKE

CarterD

HortonA

2004 Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet 36 1065 1071

8. SpilianakisCG

LaliotiMD

TownT

LeeGR

FlavellRA

2005 Interchromosomal associations between alternatively expressed loci. Nature 435 637 645

9. XuN

TsaiCL

LeeJT

2006 Transient homologous chromosome pairing marks the onset of X inactivation. Science 311 1149 1152

10. HuQ

KwonYS

NunezE

CardamoneMD

HuttKR

2008 Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules. Proc Natl Acad Sci U S A 105 19199 19204

11. CarrollJS

MeyerCA

SongJ

LiW

GeistlingerTR

2006 Genome-wide analysis of estrogen receptor binding sites. Nat Genet 38 1289 1297

12. KininisM

ChenBS

DiehlAG

IsaacsGD

ZhangT

2007 Genomic analyses of transcription factor binding, histone acetylation, and gene expression reveal mechanistically distinct classes of estrogen-regulated promoters. Mol Cell Biol 27 5090 5104

13. LaganiereJ

DebloisG

LefebvreC

BatailleAR

RobertF

2005 From the Cover: Location analysis of estrogen receptor alpha target promoters reveals that FOXA1 defines a domain of the estrogen response. Proc Natl Acad Sci U S A 102 11651 11656

14. LinCY

VegaVB

ThomsenJS

ZhangT

KongSL

2007 Whole-genome cartography of estrogen receptor alpha binding sites. PLoS Genet 3 e87 doi:10.1371/journal.pgen.0030087

15. KwonYS

Garcia-BassetsI

HuttKR

ChengCS

JinM

2007 Sensitive ChIP-DSL technology reveals an extensive estrogen receptor alpha-binding program on human gene promoters. Proc Natl Acad Sci U S A 104 4852 4857

16. HtunH

HolthLT

WalkerD

DavieJR

HagerGL

1999 Direct visualization of the human estrogen receptor alpha reveals a role for ligand in the nuclear distribution of the receptor. Mol Biol Cell 10 471 486

17. StenoienDL

ManciniMG

PatelK

AllegrettoEA

SmithCL

2000 Subnuclear trafficking of estrogen receptor-alpha and steroid receptor coactivator-1. Mol Endocrinol 14 518 534

18. MetivierR

PenotG

HubnerMR

ReidG

BrandH

2003 Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115 751 763

19. RayalaSK

den HollanderP

BalasenthilS

YangZ

BroaddusRR

2005 Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep 6 538 544

20. LeeSJ

ChaeC

WangMM

2009 p150/glued modifies nuclear estrogen receptor function. Mol Endocrinol 23 620 629

21. ManavathiB

AcconciaF

RayalaSK

KumarR

2006 An inherent role of microtubule network in the action of nuclear receptor. Proc Natl Acad Sci U S A 103 15981 15986

22. CavalliG

2007 Chromosome kissing. Curr Opin Genet Dev 17 443 450

23. KininisM

IsaacsGD

CoreLJ

HahN

KrausWL

2009 Postrecruitment regulation of RNA polymerase II directs rapid signaling responses at the promoters of estrogen target genes. Mol Cell Biol 29 1123 1133

24. SutherlandH

BickmoreWA

2009 Transcription factories: gene expression in unions? Nat Rev Genet 10 457 466

25. ChuangCH

CarpenterAE

FuchsovaB

JohnsonT

de LanerolleP

2006 Long-range directional movement of an interphase chromosome site. Curr Biol 16 825 831

26. ThomsonI

GilchristS

BickmoreWA

ChubbJR

2004 The radial positioning of chromatin is not inherited through mitosis but is established de novo in early G1. Curr Biol 14 166 172

27. ChubbJR

BoyleS

PerryP

BickmoreWA

2002 Chromatin motion is constrained by association with nuclear compartments in human cells. Curr Biol 12 439 445

28. WalterJ

SchermellehL

CremerM

TashiroS

CremerT

2003 Chromosome order in HeLa cells changes during mitosis and early G1, but is stably maintained during subsequent interphase stages. J Cell Biol 160 685 697

29. CowellJK

LaDucaJ

RossiMR

BurkhardtT

NowakNJ

2005 Molecular characterization of the t(3;9) associated with immortalization in the MCF10A cell line. Cancer Genet Cytogenet 163 23 29

30. KrystosekA

1998 Repositioning of human interphase chromosomes by nucleolar dynamics in the reverse transformation of HT1080 fibrosarcoma cells. Exp Cell Res 241 202 209

31. MoreyC

Da SilvaNR

PerryP

BickmoreWA

2007 Nuclear reorganisation and chromatin decondensation are conserved, but distinct, mechanisms linked to Hox gene activation. Development 134 909 919

32. BoyleS

GilchristS

BridgerJM

MahyNL

EllisJA

2001 The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells. Hum Mol Genet 10 211 219

33. BowieML

DietzeEC

DelrowJ

BeanGR

TrochMM

2004 Interferon-regulatory factor-1 is critical for tamoxifen-mediated apoptosis in human mammary epithelial cells. Oncogene 23 8743 8755

34. SenguptaK

BanerjeeS

SaxenaNK

JonathanNB

CampbellDR

2004 Differential expression of VEGF-A mRNA by 17beta-estradiol in breast tumor cells lacking classical ER-alpha may be mediated through a variant form of ER-alpha. Mol Cell Biochem 262 215 224

35. SouleHD

MaloneyTM

WolmanSR

PetersonWDJr

BrenzR

1990 Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res 50 6075 6086

36. JonesC

PayneJ

WellsD

DelhantyJD

LakhaniSR

2000 Comparative genomic hybridization reveals extensive variation among different MCF-7 cell stocks. Cancer Genet Cytogenet 117 153 158

37. JonssonG

StaafJ

OlssonE

HeidenbladM

Vallon-ChristerssonJ

2007 High-resolution genomic profiles of breast cancer cell lines assessed by tiling BAC array comparative genomic hybridization. Genes Chromosomes Cancer 46 543 558

38. KytolaS

RummukainenJ

NordgrenA

KarhuR

FarneboF

2000 Chromosomal alterations in 15 breast cancer cell lines by comparative genomic hybridization and spectral karyotyping. Genes Chromosomes Cancer 28 308 317

39. NeveRM

ChinK

FridlyandJ

YehJ

BaehnerFL

2006 A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 10 515 527

40. OsborneCK

HobbsK

TrentJM

1987 Biological differences among MCF-7 human breast cancer cell lines from different laboratories. Breast Cancer Res Treat 9 111 121

41. ShadeoA

LamWL

2006 Comprehensive copy number profiles of breast cancer cell model genomes. Breast Cancer Res 8 R9

42. HamptonOA

Den HollanderP

MillerCA

DelgadoDA

LiJ

2009 A sequence-level map of chromosomal breakpoints in the MCF-7 breast cancer cell line yields insights into the evolution of a cancer genome. Genome Res 19 167 177

43. ShangY

HuX

DiRenzoJ

LazarMA

BrownM

2000 Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell 103 843 852

44. BautistaS

TheilletC

1998 CCND1 and FGFR1 coamplification results in the colocalization of 11q13 and 8p12 sequences in breast tumor nuclei. Genes Chromosomes Cancer 22 268 277

45. BrunnerN

BoulayV

FojoA

FreterCE

LippmanME

1993 Acquisition of hormone-independent growth in MCF-7 cells is accompanied by increased expression of estrogen-regulated genes but without detectable DNA amplifications. Cancer Res 53 283 290

46. BrunnerN

BoysenB

JirusS

SkaarTC

Holst-HansenC

1997 MCF7/LCC9: an antiestrogen-resistant MCF-7 variant in which acquired resistance to the steroidal antiestrogen ICI 182,780 confers an early cross-resistance to the nonsteroidal antiestrogen tamoxifen. Cancer Res 57 3486 3493

47. AmanoT

SagaiT

TanabeH

MizushinaY

NakazawaH

2009 Chromosomal dynamics at the Shh locus: limb bud-specific differential regulation of competence and active transcription. Dev Cell 16 47 57

48. BrancoMR

PomboA

2006 Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations. PLoS Biol 4 e138 doi:10.1371/journal.pbio.0040138

49. HeardE

BickmoreW

2007 The ins and outs of gene regulation and chromosome territory organisation. Curr Opin Cell Biol 19 311 316

50. LaSalleJM

LalandeM

1996 Homologous association of oppositely imprinted chromosomal domains. Science 272 725 728

51. NogamiM

KohdaA

TaguchiH

NakaoM

IkemuraT

2000 Relative locations of the centromere and imprinted SNRPN gene within chromosome 15 territories during the cell cycle in HL60 cells. J Cell Sci 113 (Pt 12) 2157 2165

52. TellerK

SoloveiI

BuitingK

HorsthemkeB

CremerT

2007 Maintenance of imprinting and nuclear architecture in cycling cells. Proc Natl Acad Sci U S A 104 14970 14975

53. FussSH

OmuraM

MombaertsP

2007 Local and cis effects of the H element on expression of odorant receptor genes in mouse. Cell 130 373 384

54. CvackovaZ

MasataM

StanekD

FidlerovaH

RaskaI

2009 Chromatin position in human HepG2 cells: although being non-random, significantly changed in daughter cells. J Struct Biol 165 107 117

55. BrownJM

GreenJ

das NevesRP

WallaceHA

SmithAJ

2008 Association between active genes occurs at nuclear speckles and is modulated by chromatin environment. J Cell Biol 182 1083 1097

56. OsborneCS

ChakalovaL

MitchellJA

HortonA

WoodAL

2007 Myc dynamically and preferentially relocates to a transcription factory occupied by Igh. PLoS Biol 5 e192 doi:10.1371/journal.pbio.0050192

57. XuM

CookPR

2008 Similar active genes cluster in specialized transcription factories. J Cell Biol 181 615 623

58. Arnett-MansfieldRL

GrahamJD

HansonAR

MotePA

GompelA

2007 Focal subnuclear distribution of progesterone receptor is ligand dependent and associated with transcriptional activity. Mol Endocrinol 21 14 29

59. GrandeMA

van der KraanI

de JongL

van DrielR

1997 Nuclear distribution of transcription factors in relation to sites of transcription and RNA polymerase II. J Cell Sci 110 (Pt 15) 1781 1791

60. LarsonDR

SingerRH

ZenklusenD

2009 A single molecule view of gene expression. Trends Cell Biol 19 630 637

61. FleuryL

GerusM

LavigneAC

Richard-FoyH

BystrickyK

2008 Eliminating epigenetic barriers induces transient hormone-regulated gene expression in estrogen receptor negative breast cancer cells. Oncogene 27 4075 4085

62. NyeAC

RajendranRR

StenoienDL

ManciniMA

KatzenellenbogenBS

2002 Alteration of large-scale chromatin structure by estrogen receptor. Mol Cell Biol 22 3437 3449

63. FullwoodMJ

LiuMH

PanYF

LiuJ

XuH

2009 An oestrogen-receptor-alpha-bound human chromatin interactome. Nature 462 58 64

64. HollidayDL

BrouiletteKT

MarkertA

GordonLA

JonesJL

2009 Novel multicellular organotypic models of normal and malignant breast: tools for dissecting the role of the microenvironment in breast cancer progression. Breast Cancer Res 11 R3

65. FantesJA

BickmoreWA

FletcherJM

BallestaF

HansonIM

1992 Submicroscopic deletions at the WAGR locus, revealed by nonradioactive in situ hybridization. Am J Hum Genet 51 1286 1294

66. CremerM

GrasserF

LanctotC

MullerS

NeusserM

2008 Multicolor 3D Fluorescence In Situ Hybridization for Imaging Interphase Chromosomes. Methods Mol Biol 463 205 239

67. ChambeyronS

BickmoreWA

2004 Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. Genes Dev 18 1119 1130

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