Home LiteratureArticle Details
PMID: 18787694 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The genomic distribution and function of histone variant HTZ-1 during C. elegans embryogenesis.

PLoS genetics ·Vol. 4 ·No. 9 ·2008-09-12 ·Pages e1000187

Whittle CM, McClinic KN, Ercan S, Zhang X, Green RD, Kelly WG, Lieb JD

Abstract

In all eukaryotes, histone variants are incorporated into a subset of nucleosomes to create functionally specialized regions of chromatin. One such variant, H2A.Z, replaces histone H2A and is required for development and viability in all animals tested to date. However, the function of H2A.Z in development remains unclear. Here, we use ChIP-chip, genetic mutation, RNAi, and immunofluorescence microscopy to interrogate the function of H2A.Z (HTZ-1) during embryogenesis in Caenorhabditis elegans, a key model of metazoan development. We find that HTZ-1 is expressed in every cell of the developing embryo and is essential for normal development. The sites of HTZ-1 incorporation during embryogenesis reveal a genome wrought by developmental processes. HTZ-1 is incorporated upstream of 23% of C. elegans genes. While these genes tend to be required for development and occupied by RNA polymerase II, HTZ-1 incorporation does not specify a stereotypic transcription program. The data also provide evidence for unexpectedly widespread independent regulation of genes within operons during development; in 37% of operons, HTZ-1 is incorporated upstream of internally encoded genes. Fewer sites of HTZ-1 incorporation occur on the X chromosome relative to autosomes, which our data suggest is due to a paucity of developmentally important genes on X, rather than a direct function for HTZ-1 in dosage compensation. Our experiments indicate that HTZ-1 functions in establishing or maintaining an essential chromatin state at promoters regulated dynamically during C. elegans embryogenesis.

MeSH Terms
Animals Caenorhabditis elegans/embryology,genetics,growth & development Caenorhabditis elegans Proteins/genetics,metabolism Dosage Compensation, Genetic Embryonic Development/genetics Female Fluorescent Antibody Technique Genome, Helminth Histones/genetics,metabolism Models, Genetic Operon/genetics Promoter Regions, Genetic RNA Interference RNA Polymerase II/metabolism Transcription Initiation Site X Chromosome/metabolism
Chemicals
Caenorhabditis elegans Proteins Histones RNA Polymerase II
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Whittle Christina M
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
McClinic Karissa N
Ercan Sevinc
Zhang Xinmin
Green Roland D
Kelly William G
Lieb Jason D
Conflict of Interest

XZ and RDG are employed by NimbleGen Systems, Inc., a microarray company that might profit from the publication of this paper.

References (79)
79 references, click to expand
  1. Clustered DNA motifs mark X chromosomes for repression by a dosage compensation complex.
    Nature. 2006 Nov 30;444(7119):614-8 PMID: 17122774
  2. Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome.
    Nature. 2007 Mar 29;446(7135):572-6 PMID: 17392789
  3. Global nucleosome occupancy in yeast.
    Genome Biol. 2004;5(9):R62 PMID: 15345046
  4. Diverse chromatin remodeling genes antagonize the Rb-involved SynMuv pathways in C. elegans.
    PLoS Genet. 2006 May;2(5):e74 PMID: 16710447
  5. Pericentric heterochromatin becomes enriched with H2A.Z during early mammalian development.
    EMBO J. 2003 Apr 1;22(7):1599-607 PMID: 12660166
  6. Protein-protein Förster resonance energy transfer analysis of nucleosome core particles containing H2A and H2A.Z.
    J Mol Biol. 2007 Aug 24;371(4):971-88 PMID: 17597150
  7. A new fluorescence resonance energy transfer approach demonstrates that the histone variant H2AZ stabilizes the histone octamer within the nucleosome.
    J Biol Chem. 2004 Jun 4;279(23):24274-82 PMID: 15020582
  8. Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi.
    Curr Biol. 2001 Feb 6;11(3):171-6 PMID: 11231151
  9. Operons in eukaryotes.
    Brief Funct Genomic Proteomic. 2004 Nov;3(3):199-211 PMID: 15642184
  10. Quantitative analysis of HP1alpha binding to nucleosomal arrays.
    Methods. 2007 Mar;41(3):286-90 PMID: 17309838
  11. CEAS: cis-regulatory element annotation system.
    Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W551-4 PMID: 16845068
  12. ChIPOTle: a user-friendly tool for the analysis of ChIP-chip data.
    Genome Biol. 2005;6(11):R97 PMID: 16277752
  13. The role of histone H2Av variant replacement and histone H4 acetylation in the establishment of Drosophila heterochromatin.
    Genes Dev. 2005 Jan 1;19(1):65-76 PMID: 15630020
  14. Trans-splicing and polycistronic transcription in Caenorhabditis elegans.
    Trends Genet. 1995 Apr;11(4):132-6 PMID: 7732590
  15. The Saccharomyces cerevisiae histone H2A variant Htz1 is acetylated by NuA4.
    Genes Dev. 2006 Mar 15;20(6):660-5 PMID: 16543219
  16. Regulation of chromosome stability by the histone H2A variant Htz1, the Swr1 chromatin remodeling complex, and the histone acetyltransferase NuA4.
    Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13513-8 PMID: 15353583
  17. The nucleosome surface regulates chromatin compaction and couples it with transcriptional repression.
    Nat Struct Mol Biol. 2007 Nov;14(11):1070-6 PMID: 17965724
  18. H2A.Z stabilizes chromatin in a way that is dependent on core histone acetylation.
    J Biol Chem. 2006 Jul 21;281(29):20036-44 PMID: 16707487
  19. Nucleosome stability mediated by histone variants H3.3 and H2A.Z.
    Genes Dev. 2007 Jun 15;21(12):1519-29 PMID: 17575053
  20. Preferential occupancy of histone variant H2AZ at inactive promoters influences local histone modifications and chromatin remodeling.
    Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18385-90 PMID: 16344463
  21. xol-1: a gene that controls the male modes of both sex determination and X chromosome dosage compensation in C. elegans.
    Cell. 1988 Oct 7;55(1):167-83 PMID: 3167975
  22. H2A.Z alters the nucleosome surface to promote HP1alpha-mediated chromatin fiber folding.
    Mol Cell. 2004 Nov 19;16(4):655-61 PMID: 15546624
  23. Temporal regulation of foregut development by HTZ-1/H2A.Z and PHA-4/FoxA.
    PLoS Genet. 2006 Sep 29;2(9):e161 PMID: 17009877
  24. The MES-2/MES-3/MES-6 complex and regulation of histone H3 methylation in C. elegans.
    Curr Biol. 2004 Sep 21;14(18):1639-43 PMID: 15380065
  25. A new class of C. elegans synMuv genes implicates a Tip60/NuA4-like HAT complex as a negative regulator of Ras signaling.
    Dev Cell. 2004 Apr;6(4):563-76 PMID: 15068795
  26. GO::TermFinder--open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes.
    Bioinformatics. 2004 Dec 12;20(18):3710-5 PMID: 15297299
  27. Temporal and spatial association of histone H2A variant hv1 with transcriptionally competent chromatin during nuclear development in Tetrahymena thermophila.
    Genes Dev. 1993 Dec;7(12B):2641-51 PMID: 8276246
  28. Acetylation of H2AZ Lys 14 is associated with genome-wide gene activity in yeast.
    Genes Dev. 2006 Mar 15;20(6):711-22 PMID: 16543223
  29. Evidence for nucleosome depletion at active regulatory regions genome-wide.
    Nat Genet. 2004 Aug;36(8):900-5 PMID: 15247917
  30. Genome-wide germline-enriched and sex-biased expression profiles in Caenorhabditis elegans.
    Development. 2004 Jan;131(2):311-23 PMID: 14668411
  31. H2A.Z contributes to the unique 3D structure of the centromere.
    Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):525-30 PMID: 17194760
  32. The essential histone variant H2A.Z regulates the equilibrium between different chromatin conformational states.
    Nat Struct Biol. 2002 Mar;9(3):172-6 PMID: 11850638
  33. Analysis of histone variant H2A.Z localization and expression during early development.
    Methods Enzymol. 2004;375:239-52 PMID: 14870671
  34. Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss.
    Cell. 2005 Oct 21;123(2):219-31 PMID: 16239141
  35. The highly conserved and multifunctional NuA4 HAT complex.
    Curr Opin Genet Dev. 2004 Apr;14(2):147-54 PMID: 15196461
  36. Java Treeview--extensible visualization of microarray data.
    Bioinformatics. 2004 Nov 22;20(17):3246-8 PMID: 15180930
  37. The Yaf9 component of the SWR1 and NuA4 complexes is required for proper gene expression, histone H4 acetylation, and Htz1 replacement near telomeres.
    Mol Cell Biol. 2004 Nov;24(21):9424-36 PMID: 15485911
  38. Composition and dynamics of the Caenorhabditis elegans early embryonic transcriptome.
    Development. 2003 Mar;130(5):889-900 PMID: 12538516
  39. A conserved chromatin architecture marks and maintains the restricted germ cell lineage in worms and flies.
    Dev Cell. 2003 Nov;5(5):747-57 PMID: 14602075
  40. A global profile of germline gene expression in C. elegans.
    Mol Cell. 2000 Sep;6(3):605-16 PMID: 11030340
  41. Monoubiquitylation of H2A.Z distinguishes its association with euchromatin or facultative heterochromatin.
    Mol Cell Biol. 2007 Sep;27(18):6457-68 PMID: 17636032
  42. Operons as a common form of chromosomal organization in C. elegans.
    Nature. 1994 Nov 17;372(6503):270-2 PMID: 7969472
  43. Operons in C. elegans: polycistronic mRNA precursors are processed by trans-splicing of SL2 to downstream coding regions.
    Cell. 1993 May 7;73(3):521-32 PMID: 8098272
  44. The H2A.Z/H2B dimer is unstable compared to the dimer containing the major H2A isoform.
    Protein Sci. 2005 Feb;14(2):514-22 PMID: 15632282
  45. Trans-splicing and operons.
    WormBook. 2005 Jun 25;:1-9 PMID: 18050426
  46. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi.
    Nature. 2003 Jan 16;421(6920):231-7 PMID: 12529635
  47. SAS-mediated acetylation of histone H4 Lys 16 is required for H2A.Z incorporation at subtelomeric regions in Saccharomyces cerevisiae.
    Genes Dev. 2006 Sep 15;20(18):2507-12 PMID: 16980580
  48. A chromatin landmark and transcription initiation at most promoters in human cells.
    Cell. 2007 Jul 13;130(1):77-88 PMID: 17632057
  49. Gene-breaking transposon mutagenesis reveals an essential role for histone H2afza in zebrafish larval development.
    Mech Dev. 2006 Jul;123(7):513-29 PMID: 16859902
  50. Unique residues on the H2A.Z containing nucleosome surface are important for Xenopus laevis development.
    J Biol Chem. 2004 Oct 15;279(42):43815-20 PMID: 15299007
  51. Maintenance of C. elegans.
    WormBook. 2006 Feb 11;:1-11 PMID: 18050451
  52. Histone variant H2A.Z is required for early mammalian development.
    Curr Biol. 2001 Aug 7;11(15):1183-7 PMID: 11516949
  53. RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo.
    Nat Genet. 2007 Dec;39(12):1512-6 PMID: 17994019
  54. RNA polymerase is poised for activation across the genome.
    Nat Genet. 2007 Dec;39(12):1507-11 PMID: 17994021
  55. High-resolution profiling of histone methylations in the human genome.
    Cell. 2007 May 18;129(4):823-37 PMID: 17512414
  56. H2A.Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional state.
    PLoS Biol. 2007 Apr;5(4):e81 PMID: 17373856
  57. Effects of histone acetylation, ubiquitination and variants on nucleosome stability.
    Biochem J. 1993 Dec 15;296 ( Pt 3):737-44 PMID: 8280071
  58. Identification and analysis of internal promoters in Caenorhabditis elegans operons.
    Genome Res. 2007 Oct;17(10):1478-85 PMID: 17712020
  59. Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4.
    Science. 2002 Feb 1;295(5556):821-5 PMID: 11823633
  60. Cluster analysis and display of genome-wide expression patterns.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 PMID: 9843981
  61. hv1 is an evolutionarily conserved H2A variant that is preferentially associated with active genes.
    J Biol Chem. 1986 Feb 5;261(4):1941-8 PMID: 3944120
  62. Regions of variant histone His2AvD required for Drosophila development.
    Nature. 1999 Jun 17;399(6737):694-7 PMID: 10385122
  63. p21 transcription is regulated by differential localization of histone H2A.Z.
    Genes Dev. 2007 Aug 1;21(15):1869-81 PMID: 17671089
  64. The replacement histone H2A.Z in a hyperacetylated form is a feature of active genes in the chicken.
    Nucleic Acids Res. 2005 Oct 04;33(17):5633-9 PMID: 16204459
  65. Timing of the appearance of macronuclear-specific histone variant hv1 and gene expression in developing new macronuclei of Tetrahymena thermophila.
    J Cell Biol. 1984 Jun;98(6):2107-17 PMID: 6373790
  66. Repression of gene expression in the embryonic germ lineage of C. elegans.
    Nature. 1996 Aug 22;382(6593):713-6 PMID: 8751441
  67. H2A.Z is required for global chromatin integrity and for recruitment of RNA polymerase II under specific conditions.
    Mol Cell Biol. 2001 Sep;21(18):6270-9 PMID: 11509669
  68. RSF governs silent chromatin formation via histone H2Av replacement.
    PLoS Genet. 2008 Feb 29;4(2):e1000011 PMID: 18454204
  69. Genome-wide analysis of developmental and sex-regulated gene expression profiles in Caenorhabditis elegans.
    Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):218-23 PMID: 11134517
  70. A zebrafish histone variant H2A.F/Z and a transgenic H2A.F/Z:GFP fusion protein for in vivo studies of embryonic development.
    Dev Genes Evol. 2001 Dec;211(12):603-10 PMID: 11819118
  71. X chromosome repression by localization of the C. elegans dosage compensation machinery to sites of transcription initiation.
    Nat Genet. 2007 Mar;39(3):403-8 PMID: 17293863
  72. Caenorhabditis elegans compensates for the difference in X chromosome dosage between the sexes by regulating transcript levels.
    Cell. 1986 Dec 26;47(6):871-81 PMID: 3779843
  73. The C. elegans pharynx: a model for organogenesis.
    WormBook. 2007 Jan 22;:1-26 PMID: 18050503
  74. A histone variant, H2AvD, is essential in Drosophila melanogaster.
    Mol Biol Cell. 1992 Jun;3(6):593-602 PMID: 1498368
  75. Histone H2A.Z is widely but nonrandomly distributed in chromosomes of Drosophila melanogaster.
    J Biol Chem. 2000 Jul 28;275(30):23267-72 PMID: 10801889
  76. Nucleosome organization in the Drosophila genome.
    Nature. 2008 May 15;453(7193):358-62 PMID: 18408708
  77. Variant histone H2A.Z is globally localized to the promoters of inactive yeast genes and regulates nucleosome positioning.
    PLoS Biol. 2005 Dec;3(12):e384 PMID: 16248679
  78. Genome-wide map of nucleosome acetylation and methylation in yeast.
    Cell. 2005 Aug 26;122(4):517-27 PMID: 16122420
  79. Histone variant H2A.Z marks the 5' ends of both active and inactive genes in euchromatin.
    Cell. 2005 Oct 21;123(2):233-48 PMID: 16239142
Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1000187
Published
2008-09-12
Epub
2008-00-12
Pages
e1000187
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2522285
Subset
IM
Grants
NICHD NIH HHS · T32 HD046369 · United States
NHGRI NIH HHS · 1-U01-HG004270-01 · United States
NIGMS NIH HHS · GM63102 · United States
NHGRI NIH HHS · U01 HG004270 · United States
NHGRI NIH HHS · U01 HG004270-01 · United States
NHGRI NIH HHS · U01 HG004270-02 · United States
NIGMS NIH HHS · R01 GM063102 · United States
External Links
PubMed source DOI: 10.1371/journal.pgen.1000187 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2