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Dynamic Chromatin Organization during Foregut Development Mediated by the Organ Selector Gene PHA-4/FoxA


Central regulators of cell fate, or selector genes, establish the identity of cells by direct regulation of large cohorts of genes. In Caenorhabditis elegans, foregut (or pharynx) identity relies on the FoxA transcription factor PHA-4, which activates different sets of target genes at various times and in diverse cellular environments. An outstanding question is how PHA-4 distinguishes between target genes for appropriate transcriptional control. We have used the Nuclear Spot Assay and GFP reporters to examine PHA-4 interactions with target promoters in living embryos and with single cell resolution. While PHA-4 was found throughout the digestive tract, binding and activation of pharyngeally expressed promoters was restricted to a subset of pharyngeal cells and excluded from the intestine. An RNAi screen of candidate nuclear factors identified emerin (emr-1) as a negative regulator of PHA-4 binding within the pharynx, but emr-1 did not modulate PHA-4 binding in the intestine. Upon promoter association, PHA-4 induced large-scale chromatin de-compaction, which, we hypothesize, may facilitate promoter access and productive transcription. Our results reveal two tiers of PHA-4 regulation. PHA-4 binding is prohibited in intestinal cells, preventing target gene expression in that organ. PHA-4 binding within the pharynx is limited by the nuclear lamina component EMR-1/emerin. The data suggest that association of PHA-4 with its targets is a regulated step that contributes to promoter selectivity during organ formation. We speculate that global re-organization of chromatin architecture upon PHA-4 binding promotes competence of pharyngeal gene transcription and, by extension, foregut development.


Vyšlo v časopise: Dynamic Chromatin Organization during Foregut Development Mediated by the Organ Selector Gene PHA-4/FoxA. PLoS Genet 6(8): e32767. doi:10.1371/journal.pgen.1001060
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001060

Souhrn

Central regulators of cell fate, or selector genes, establish the identity of cells by direct regulation of large cohorts of genes. In Caenorhabditis elegans, foregut (or pharynx) identity relies on the FoxA transcription factor PHA-4, which activates different sets of target genes at various times and in diverse cellular environments. An outstanding question is how PHA-4 distinguishes between target genes for appropriate transcriptional control. We have used the Nuclear Spot Assay and GFP reporters to examine PHA-4 interactions with target promoters in living embryos and with single cell resolution. While PHA-4 was found throughout the digestive tract, binding and activation of pharyngeally expressed promoters was restricted to a subset of pharyngeal cells and excluded from the intestine. An RNAi screen of candidate nuclear factors identified emerin (emr-1) as a negative regulator of PHA-4 binding within the pharynx, but emr-1 did not modulate PHA-4 binding in the intestine. Upon promoter association, PHA-4 induced large-scale chromatin de-compaction, which, we hypothesize, may facilitate promoter access and productive transcription. Our results reveal two tiers of PHA-4 regulation. PHA-4 binding is prohibited in intestinal cells, preventing target gene expression in that organ. PHA-4 binding within the pharynx is limited by the nuclear lamina component EMR-1/emerin. The data suggest that association of PHA-4 with its targets is a regulated step that contributes to promoter selectivity during organ formation. We speculate that global re-organization of chromatin architecture upon PHA-4 binding promotes competence of pharyngeal gene transcription and, by extension, foregut development.


Zdroje

1. MannRS

CarrollSB

2002 Molecular mechanisms of selector gene function and evolution. Curr Opin Genet Dev 12 592 600

2. GaudetJ

MangoSE

2002 Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4. Science 295 821 825

3. FurlongEE

AndersenEC

NullB

WhiteKP

ScottMP

2001 Patterns of gene expression during Drosophila mesoderm development. Science 293 1629 1633

4. TapscottSJ

2005 The circuitry of a master switch: Myod and the regulation of skeletal muscle gene transcription. Development 132 2685 2695

5. LiangZ

BigginMD

1998 Eve and ftz regulate a wide array of genes in blastoderm embryos: the selector homeoproteins directly or indirectly regulate most genes in Drosophila. Development 125 4471 4482

6. ZeitlingerJ

ZinzenRP

StarkA

KellisM

ZhangH

2007 Whole-genome ChIP-chip analysis of Dorsal, Twist, and Snail suggests integration of diverse patterning processes in the Drosophila embryo. Genes Dev 21 385 390

7. SandmannT

GirardotC

BrehmeM

TongprasitW

StolcV

2007 A core transcriptional network for early mesoderm development in Drosophila melanogaster. Genes Dev 21 436 449

8. CaoY

YaoZ

SarkarD

LawrenceM

SanchezGJ

2010 Genome-wide MyoD binding in skeletal muscle cells: a potential for broad cellular reprogramming. Dev Cell 18 662 674

9. HornerMA

QuintinS

DomeierME

KimbleJ

LabouesseM

1998 pha-4, an HNF-3 homologue, specifies pharyngeal organ identity in Caenorhabditis elegans. Genes Dev 12 1947 1952

10. KalbJM

LauKK

GoszczynskiB

FukushigeT

MoonsD

1998 pha-4 is Ce-fkh-1, a fork head/HNF-3alpha,beta,gamma homolog that functions in organogenesis of the C. elegans pharynx. Development 125 2171 2180

11. KieferJC

SmithPA

MangoSE

2007 PHA-4/FoxA cooperates with TAM-1/TRIM to regulate cell fate restriction in the C. elegans foregut. Dev Biol 303 611 624

12. MangoSE

LambieEJ

KimbleJ

1994 The pha-4 gene is required to generate the pharyngeal primordium of Caenorhabditis elegans. Development 120 3019 3031

13. AoW

GaudetJ

KentWJ

MuttumuS

MangoSE

2004 Environmentally induced foregut remodeling by PHA-4/FoxA and DAF-12/NHR. Science 305 1743 1746

14. ChenD

RiddleDL

2008 Function of the PHA-4/FOXA transcription factor during C. elegans post-embryonic development. BMC Dev Biol 8 26

15. UpdikeDL

MangoSE

2007 Genetic suppressors of Caenorhabditis elegans pha-4/FoxA identify the predicted AAA helicase ruvb-1/RuvB. Genetics 177 819 833

16. PanowskiSH

WolffS

AguilaniuH

DurieuxJ

DillinA

2007 PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans. Nature 447 550 555

17. SheafferKL

UpdikeDL

MangoSE

2008 The Target of Rapamycin pathway antagonizes pha-4/FoxA to control development and aging. Curr Biol 18 1355 1364

18. GaudetJ

MuttumuS

HornerM

MangoSE

2004 Whole-genome analysis of temporal gene expression during foregut development. PLoS Biol 2 e352 doi:10.1371/journal.pbio.0020352

19. ZhongM

NiuW

LuZJ

SarovM

MurrayJI

2010 Genome-wide identification of binding sites defines distinct functions for Caenorhabditis elegans PHA-4/FOXA in development and environmental response. PLoS Genet 6 e1000848 doi:10.1371/journal.pgen.1000848

20. ThatcherJD

HaunC

OkkemaPG

1999 The DAF-3 Smad binds DNA and represses gene expression in the Caenorhabditis elegans pharynx. Development 126 97 107

21. ThatcherJD

FernandezAP

Beaster-JonesL

HaunC

OkkemaPG

2001 The Caenorhabditis elegans peb-1 gene encodes a novel DNA-binding protein involved in morphogenesis of the pharynx, vulva, and hindgut. Dev Biol 229 480 493

22. DeplanckeB

MukhopadhyayA

AoW

ElewaAM

GroveCA

2006 A gene-centered C. elegans protein-DNA interaction network. Cell 125 1193 1205

23. OkkemaPG

HaE

HaunC

ChenW

FireA

1997 The Caenorhabditis elegans NK-2 homeobox gene ceh-22 activates pharyngeal muscle gene expression in combination with pha-1 and is required for normal pharyngeal development. Development 124 3965 3973

24. RaharjoI

GaudetJ

2007 Gland-specific expression of C. elegans hlh-6 requires the combinatorial action of three distinct promoter elements. Dev Biol 302 295 308

25. RasmussenJP

EnglishK

TenlenJR

PriessJR

2008 Notch signaling and morphogenesis of single-cell tubes in the C. elegans digestive tract. Dev Cell 14 559 569

26. CasolariJM

BrownCR

KomiliS

WestJ

HieronymusH

2004 Genome-wide localization of the nuclear transport machinery couples transcriptional status and nuclear organization. Cell 117 427 439

27. TaddeiA

Van HouweG

HedigerF

KalckV

CubizollesF

2006 Nuclear pore association confers optimal expression levels for an inducible yeast gene. Nature 441 774 778

28. BricknerJH

WalterP

2004 Gene recruitment of the activated INO1 locus to the nuclear membrane. PLoS Biol 2 e342 doi:10.1371/journal.pbio.0020342

29. CabalGG

GenovesioA

Rodriguez-NavarroS

ZimmerC

GadalO

2006 SAGA interacting factors confine sub-diffusion of transcribed genes to the nuclear envelope. Nature 441 770 773

30. DieppoisG

IglesiasN

StutzF

2006 Cotranscriptional recruitment to the mRNA export receptor Mex67p contributes to nuclear pore anchoring of activated genes. Mol Cell Biol 26 7858 7870

31. MargalitA

NeufeldE

FeinsteinN

WilsonKL

PodbilewiczB

2007 Barrier to autointegration factor blocks premature cell fusion and maintains adult muscle integrity in C. elegans. J Cell Biol 178 661 673

32. NiliE

CojocaruGS

KalmaY

GinsbergD

CopelandNG

2001 Nuclear membrane protein LAP2beta mediates transcriptional repression alone and together with its binding partner GCL (germ-cell-less). J Cell Sci 114 3297 3307

33. SomechR

ShaklaiS

GellerO

AmariglioN

SimonAJ

2005 The nuclear-envelope protein and transcriptional repressor LAP2beta interacts with HDAC3 at the nuclear periphery, and induces histone H4 deacetylation. J Cell Sci 118 4017 4025

34. LiuJ

Rolef Ben-ShaharT

RiemerD

TreininM

SpannP

2000 Essential roles for Caenorhabditis elegans lamin gene in nuclear organization, cell cycle progression, and spatial organization of nuclear pore complexes. Mol Biol Cell 11 3937 3947

35. DechatT

PfleghaarK

SenguptaK

ShimiT

ShumakerDK

2008 Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev 22 832 853

36. GruenbaumY

LeeKK

LiuJ

CohenM

WilsonKL

2002 The expression, lamin-dependent localization and RNAi depletion phenotype for emerin in C. elegans. J Cell Sci 115 923 929

37. SproulD

GilbertN

BickmoreWA

2005 The role of chromatin structure in regulating the expression of clustered genes. Nat Rev Genet 6 775 781

38. FinlanLE

SproulD

ThomsonI

BoyleS

KerrE

2008 Recruitment to the nuclear periphery can alter expression of genes in human cells. PLoS Genet 4 e1000039 doi:10.1371/journal.pgen.1000039

39. ReddyKL

ZulloJM

BertolinoE

SinghH

2008 Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 452 243 247

40. KumaranRI

SpectorDL

2008 A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence. J Cell Biol 180 51 65

41. RagoczyT

BenderMA

TellingA

ByronR

GroudineM

2006 The locus control region is required for association of the murine beta-globin locus with engaged transcription factories during erythroid maturation. Genes Dev 20 1447 1457

42. RiemerD

DodemontH

WeberK

1993 A nuclear lamin of the nematode Caenorhabditis elegans with unusual structural features; cDNA cloning and gene organization. Eur J Cell Biol 62 214 223

43. LiuJ

LeeKK

Segura-TottenM

NeufeldE

WilsonKL

2003 MAN1 and emerin have overlapping function(s) essential for chromosome segregation and cell division in Caenorhabditis elegans. Proc Natl Acad Sci U S A 100 4598 4603

44. OegemaK

HymanAA

2006 Cell division. WormBook 1 40

45. LeeKK

GruenbaumY

SpannP

LiuJ

WilsonKL

2000 C. elegans nuclear envelope proteins emerin, MAN1, lamin, and nucleoporins reveal unique timing of nuclear envelope breakdown during mitosis. Mol Biol Cell 11 3089 3099

46. MargalitA

Segura-TottenM

GruenbaumY

WilsonKL

2005 Barrier-to-autointegration factor is required to segregate and enclose chromosomes within the nuclear envelope and assemble the nuclear lamina. Proc Natl Acad Sci U S A 102 3290 3295

47. ZhengR

GhirlandoR

LeeMS

MizuuchiK

KrauseM

2000 Barrier-to-autointegration factor (BAF) bridges DNA in a discrete, higher-order nucleoprotein complex. Proc Natl Acad Sci U S A 97 8997 9002

48. YuzyukT

FakhouriTH

KieferJ

MangoSE

2009 The polycomb complex protein mes-2/E(z) promotes the transition from developmental plasticity to differentiation in C. elegans embryos. Dev Cell 16 699 710

49. BelmontAS

StraightAF

1998 In vivo visualization of chromosomes using lac operator-repressor binding. Trends Cell Biol 8 121 124

50. CarmiI

KopczynskiJB

MeyerBJ

1998 The nuclear hormone receptor SEX-1 is an X-chromosome signal that determines nematode sex. Nature 396 168 173

51. Gonzalez-SerricchioAS

SternbergPW

2006 Visualization of C. elegans transgenic arrays by green fluorescent protein (GFP). BMC Genet 7 36

52. FukushigeT

HendzelMJ

Bazett-JonesDP

McGheeJD

1999 Direct visualization of the elt-2 gut-specific GATA factor binding to a target promoter inside the living Caenorhabditis elegans embryo. Proc Natl Acad Sci U S A 96 11883 11888

53. CirilloLA

LinFR

CuestaI

FriedmanD

JarnikM

2002 Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4. Mol Cell 9 279 289

54. LupienM

EeckhouteJ

MeyerCA

WangQ

ZhangY

2008 FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. Cell 132 958 970

55. SunK

CoicE

ZhouZ

DurrensP

HaberJE

2002 Saccharomyces forkhead protein Fkh1 regulates donor preference during mating-type switching through the recombination enhancer. Genes Dev 16 2085 2096

56. OkkemaPG

KrauseM

2005 Transcriptional regulation. WormBook 1 40

57. EpsteinHF

WaterstonRH

BrennerS

1974 A mutant affecting the heavy chain of myosin in Caenorhabditis elegans. J Mol Biol 90 291 300

58. KaltenbachL

HornerMA

RothmanJH

MangoSE

2000 The TBP-like factor CeTLF is required to activate RNA polymerase II transcription during C. elegans embryogenesis. Mol Cell 6 705 713

59. KellyWG

XuS

MontgomeryMK

FireA

1997 Distinct requirements for somatic and germline expression of a generally expressed Caernorhabditis elegans gene. Genetics 146 227 238

60. EvansTC

2006 Transformation and microinjection. WormBook doi/10.1895/wormbook.1.108.1

61. GualdiR

BossardP

ZhengM

HamadaY

ColemanJR

1996 Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control. Genes Dev 10 1670 1682

62. MangoSE

2007 The C. elegans pharynx: a model for organogenesis. WormBook doi/10.1895/wormbook.1.7.1

63. UpdikeDL

MangoSE

2006 Temporal regulation of foregut development by HTZ-1/H2A.Z and PHA-4/FoxA. PLoS Genet 2 e161 doi:10.1371/journal.pgen.0020161

64. ZaretKS

2002 Regulatory phases of early liver development: paradigms of organogenesis. Nat Rev Genet 3 499 512

65. ZaretK

1999 Developmental competence of the gut endoderm: genetic potentiation by GATA and HNF3/fork head proteins. Dev Biol 209 1 10

66. MangoSE

2009 The molecular basis of organ formation: insights from the C. elegans foregut. Annu Rev Cell Dev Biol 25 597 628

67. ChambeyronS

BickmoreWA

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

68. WilliamsSK

TylerJK

2007 Transcriptional regulation by chromatin disassembly and reassembly. Curr Opin Genet Dev 17 88 93

69. MullerWG

WalkerD

HagerGL

McNallyJG

2001 Large-scale chromatin decondensation and recondensation regulated by transcription from a natural promoter. J Cell Biol 154 33 48

70. AzzariaM

GoszczynskiB

ChungMA

KalbJM

McGheeJD

1996 A fork head/HNF-3 homolog expressed in the pharynx and intestine of the Caenorhabditis elegans embryo. Developmental Biology 178 289 303

71. TerranovaR

PujolN

FasanoL

DjabaliM

2002 Characterisation of set-1, a conserved PR/SET domain gene in Caenorhabditis elegans. Gene 292 33 41

72. GrishokA

SinskeyJL

SharpPA

2005 Transcriptional silencing of a transgene by RNAi in the soma of C. elegans. Genes Dev 19 683 696

73. AndersenEC

HorvitzHR

2007 Two C. elegans histone methyltransferases repress lin-3 EGF transcription to inhibit vulval development. Development 134 2991 2999

74. BesslerJB

AndersenEC

VilleneuveAM

2010 Differential localization and independent acquisition of the H3K9me2 and H3K9me3 chromatin modifications in the Caenorhabditis elegans adult germ line. PLoS Genet 6 e1000830 doi:10.1371/journal.pgen.1000830

75. GruenbaumY

WilsonKL

HarelA

GoldbergM

CohenM

2000 Review: nuclear lamins—structural proteins with fundamental functions. J Struct Biol 129 313 323

76. SchanerCE

KellyWG

2006 Germline chromatin. WormBook 1 14

77. CarrollJS

LiuXS

BrodskyAS

LiW

MeyerCA

2005 Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. Cell 122 33 43

78. ErcanS

ReeseJC

WorkmanJL

SimpsonRT

2005 Yeast recombination enhancer is stimulated by transcription activation. Mol Cell Biol 25 7976 7987

79. StinchcombDT

ShawJE

CarrSH

HirshD

1985 Extrachromosomal DNA transformation of Caenorhabditis elegans. Mol Cell Biol 5 3484 3496

80. GruenbaumY

MargalitA

GoldmanRD

ShumakerDK

WilsonKL

2005 The nuclear lamina comes of age. Nat Rev Mol Cell Biol 6 21 31

81. FukushigeT

KrauseM

2005 The myogenic potency of HLH-1 reveals wide-spread developmental plasticity in early C. elegans embryos. Development 132 1795 1805

82. CairnsBR

2007 Chromatin remodeling: insights and intrigue from single-molecule studies. Nat Struct Mol Biol 14 989 996

83. BoegerH

GriesenbeckJ

KornbergRD

2008 Nucleosome retention and the stochastic nature of promoter chromatin remodeling for transcription. Cell 133 716 726

84. PeteschSJ

LisJT

2008 Rapid, transcription-independent loss of nucleosomes over a large chromatin domain at Hsp70 loci. Cell 134 74 84

85. LinR

HillRJ

PriessJR

1998 POP-1 and anterior-posterior fate decisions in C. elegans embryos. Cell 92 229 239

86. KalettaT

SchnabelH

SchnabelR

1997 Binary specification of the embryonic lineage in Caenorhabditis elegans. Nature 390 294 298

87. KorswagenHC

HermanMA

CleversHC

2000 Distinct beta-catenins mediate adhesion and signalling functions in C. elegans. Nature 406 527 532

88. OrkinSH

1992 GATA-binding transcription factors in hematopoietic cells. Blood 80 575 581

89. PedonePV

OmichinskiJG

NonyP

TrainorC

GronenbornAM

1997 The N-terminal fingers of chicken GATA-2 and GATA-3 are independent sequence-specific DNA binding domains. EMBO J 16 2874 2882

90. BrennerS

1974 The genetics of Caenorhabditis elegans. Genetics 77 71 94

91. GriesbeckO

BairdGS

CampbellRE

ZachariasDA

TsienRY

2001 Reducing the environmental sensitivity of yellow fluorescent protein. Mechanism and applications. J Biol Chem 276 29188 29194

92. HopeIA

1991 “Promoter trapping” in Caenorhabditis elegans. Development 113 399 408

93. MelloCC

KramerJM

StinchcombD

AmbrosV

1991 Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J 10 3959 3970

94. KaltenbachLS

UpdikeDL

MangoSE

2005 Contribution of the amino and carboxyl termini for PHA-4/FoxA function in Caenorhabditis elegans. Dev Dyn 234 346 354

95. PrussRM

MirskyR

RaffMC

ThorpeR

DowdingAJ

1981 All classes of intermediate filaments share a common antigenic determinant defined by a monoclonal antibody. Cell 27 419 428

96. StraightAF

BelmontAS

RobinettCC

MurrayAW

1996 GFP tagging of budding yeast chromosomes reveals that protein-protein interactions can mediate sister chromatid cohesion. Curr Biol 6 1599 1608

97. TimmonsL

CourtDL

FireA

2001 Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263 103 112

98. KamathRS

FraserAG

DongY

PoulinG

DurbinR

2003 Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421 231 237

99. TabaraH

MotohashiT

KoharaY

1996 A multi-well version of in situ hybridization on whole mount embryos of Caenorhabditis elegans. Nucleic Acids Res 24 2119 2124

100. AltunZF

HerndonL.A.

CrockerC.

LintsR.

HallD.H.

2002–2009 WormAtlas http://wwwwormatlasorg

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