Home LiteratureArticle Details
PMID: 19515973 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Stalled Hox promoters as chromosomal boundaries.

Genes & development ·Vol. 23 ·No. 13 ·2009-07-01 ·Pages 1505-9

Chopra VS, Cande J, Hong JW, Levine M

Abstract

Many developmental control genes contain stalled RNA Polymerase II (Pol II) in the early Drosophila embryo, including four of the eight Hox genes. Here, we present evidence that the stalled Hox promoters possess an intrinsic insulator activity. The enhancer-blocking activities of these promoters are dependent on general transcription factors that inhibit Pol II elongation, including components of the DSIF and NELF complexes. The activities of conventional insulators are also impaired in embryos containing reduced levels of DSIF and NELF. Thus, promoter-proximal stalling factors might help promote insulator-promoter interactions. We propose that stalled promoters help organize gene complexes within chromosomal loop domains.

MeSH Terms
Animals Chromosomes/genetics Drosophila melanogaster/embryology,genetics Embryo, Nonmammalian/embryology,enzymology,metabolism Insulator Elements/physiology Peptide Elongation Factors/metabolism Promoter Regions, Genetic/physiology Protein Binding RNA Polymerase II/metabolism
Chemicals
Peptide Elongation Factors RNA Polymerase II
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Chopra Vivek S
Department of Molecular and Cellular Biology, Division of Genetics, Genomics, and Development, University of California at Berkeley, Berkeley, California 94720, USA. vschopra@berkeley.edu
Cande Jessica
Hong Joung-Woo
Levine Michael
References (39)
39 references, click to expand
  1. Regulation of Hox gene activity by transcriptional elongation in Drosophila.
    Curr Biol. 2009 Apr 28;19(8):688-93 PMID: 19345103
  2. Spt5 and spt6 are associated with active transcription and have characteristics of general elongation factors in D. melanogaster.
    Genes Dev. 2000 Oct 15;14(20):2623-34 PMID: 11040216
  3. The dorsal morphogen gradient regulates the mesoderm determinant twist in early Drosophila embryos.
    Genes Dev. 1991 Oct;5(10):1881-91 PMID: 1655572
  4. NELF and GAGA factor are linked to promoter-proximal pausing at many genes in Drosophila.
    Mol Cell Biol. 2008 May;28(10):3290-300 PMID: 18332113
  5. Protein:protein interactions and the pairing of boundary elements in vivo.
    Genes Dev. 2003 Mar 1;17(5):664-75 PMID: 12629048
  6. The bithorax complex: the first fifty years.
    Int J Dev Biol. 1998;42(3):403-15 PMID: 9654025
  7. Promoter targeting sequence mediates enhancer interference in the Drosophila embryo.
    Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3237-42 PMID: 17307884
  8. The Fab-8 boundary defines the distal limit of the bithorax complex iab-7 domain and insulates iab-7 from initiation elements and a PRE in the adjacent iab-8 domain.
    Development. 2000 Feb;127(4):779-90 PMID: 10648236
  9. A global control region defines a chromosomal regulatory landscape containing the HoxD cluster.
    Cell. 2003 May 2;113(3):405-17 PMID: 12732147
  10. Breaking barriers to transcription elongation.
    Nat Rev Mol Cell Biol. 2006 Aug;7(8):557-67 PMID: 16936696
  11. The Mcp element mediates stable long-range chromosome-chromosome interactions in Drosophila.
    Mol Biol Cell. 2006 May;17(5):2158-65 PMID: 16495335
  12. The enhancer-blocking activity of the Fab-7 boundary from the Drosophila bithorax complex requires GAGA-factor-binding sites.
    Genetics. 2004 Nov;168(3):1371-84 PMID: 15579691
  13. Active promoters and insulators are marked by the centrosomal protein 190.
    EMBO J. 2009 Apr 8;28(7):877-88 PMID: 19229299
  14. Chromatin insulators: regulatory mechanisms and epigenetic inheritance.
    Mol Cell. 2008 Oct 10;32(1):1-9 PMID: 18851828
  15. NELF-mediated stalling of Pol II can enhance gene expression by blocking promoter-proximal nucleosome assembly.
    Genes Dev. 2008 Jul 15;22(14):1921-33 PMID: 18628398
  16. Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex.
    Nat Cell Biol. 2007 Oct;9(10):1167-74 PMID: 17828248
  17. Genetic organization of Drosophila bithorax complex.
    Nature. 1985 Jan 10-18;313(5998):108-13 PMID: 3917555
  18. Interplay between positive and negative elongation factors: drawing a new view of DRB.
    Genes Cells. 1998 Jan;3(1):9-15 PMID: 9581978
  19. A new homeotic mutation in the Drosophila bithorax complex removes a boundary separating two domains of regulation.
    EMBO J. 1990 Aug;9(8):2579-85 PMID: 1973385
  20. Probing long-distance regulatory interactions in the Drosophila melanogaster bithorax complex using Dam identification.
    Nat Genet. 2006 Aug;38(8):931-5 PMID: 16823379
  21. Pairing between gypsy insulators facilitates the enhancer action in trans throughout the Drosophila genome.
    Mol Cell Biol. 2005 Nov;25(21):9283-91 PMID: 16227580
  22. Regulation of even-skipped stripe 2 in the Drosophila embryo.
    EMBO J. 1992 Nov;11(11):4047-57 PMID: 1327756
  23. Molecular and genetic organization of the antennapedia gene complex of Drosophila melanogaster.
    Adv Genet. 1990;27:309-62 PMID: 1971986
  24. Silencers in abdominal-B, a homeotic Drosophila gene.
    EMBO J. 1993 Apr;12(4):1415-25 PMID: 8096812
  25. The Fab-7 element of the bithorax complex attenuates enhancer-promoter interactions in the Drosophila embryo.
    Genes Dev. 1996 Dec 15;10(24):3195-201 PMID: 8985187
  26. A novel cis-regulatory element, the PTS, mediates an anti-insulator activity in the Drosophila embryo.
    Cell. 1999 Dec 10;99(6):567-75 PMID: 10612393
  27. The role of insulator elements in defining domains of gene expression.
    Curr Opin Genet Dev. 1997 Apr;7(2):242-8 PMID: 9115431
  28. Molecular characterization of Drosophila NELF.
    Nucleic Acids Res. 2005 Mar 01;33(4):1269-79 PMID: 15741180
  29. RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo.
    Nat Genet. 2007 Dec;39(12):1512-6 PMID: 17994019
  30. RNA polymerase is poised for activation across the genome.
    Nat Genet. 2007 Dec;39(12):1507-11 PMID: 17994021
  31. DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs.
    Genes Dev. 1998 Feb 1;12(3):343-56 PMID: 9450929
  32. GAGA mediates the enhancer blocking activity of the eve promoter in the Drosophila embryo.
    Genes Dev. 1998 Nov 1;12(21):3325-30 PMID: 9808619
  33. Genome-wide mapping of boundary element-associated factor (BEAF) binding sites in Drosophila melanogaster links BEAF to transcription.
    Mol Cell Biol. 2009 Jul;29(13):3556-68 PMID: 19380483
  34. The abdominal-B promoter tethering element mediates promoter-enhancer specificity at the Drosophila bithorax complex.
    Fly (Austin). 2007 Nov-Dec;1(6):337-9 PMID: 18504507
  35. The Trithorax-like gene encodes the Drosophila GAGA factor.
    Nature. 1994 Oct 27;371(6500):806-8 PMID: 7935842
  36. Making connections: boundaries and insulators in Drosophila.
    Curr Opin Genet Dev. 2007 Oct;17(5):394-9 PMID: 17904351
  37. Study of the functional interaction between Mcp insulators from the Drosophila bithorax complex: effects of insulator pairing on enhancer-promoter communication.
    Mol Cell Biol. 2007 Apr;27(8):3035-43 PMID: 17283051
  38. Long-distance interactions between enhancers and promoters.
    FEBS J. 2005 Jul;272(13):3253-9 PMID: 15978032
  39. Functional interaction between the Fab-7 and Fab-8 boundaries and the upstream promoter region in the Drosophila Abd-B gene.
    Mol Cell Biol. 2008 Jun;28(12):4188-95 PMID: 18426914
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
1549-5477
Published
2009-07-01
Epub
2009-00-10
Pages
1505-9
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2704471
Subset
IM
Grants
NIGMS NIH HHS · R01 GM034431 · United States
NIGMS NIH HHS · GM34431 · United States
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: product@genelibs.com