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PMID: 18195046 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

macroH2A1-dependent silencing of endogenous murine leukemia viruses.

Molecular and cellular biology ·Vol. 28 ·No. 6 ·2008-03-00 ·Pages 2059-65

Changolkar LN, Singh G, Pehrson JR

Abstract

We show that macroH2A1 histone variants are important for repressing the expression of endogenous murine leukemia viruses (MLVs) in mouse liver. Intact MLV proviruses and proviruses with deletions in env were nearly silent in normal mouse liver and showed substantial derepression in macroH2A1 knockout liver. In contrast, MLV proviruses with a deletion in the 5' end of pro-pol were expressed in normal liver and showed relatively low levels of derepression in knockout liver. macroH2A1 nucleosomes were enriched on endogenous MLVs, with the highest enrichment occurring on the 5' end of pro-pol. The absence of macroH2A1 also led to a localized loss of DNA methylation on the 5' ends of MLV proviruses. These results demonstrate that macroH2A1 histones have a significant role in silencing endogenous MLVs in vivo and suggest that specific internal MLV sequences are targeted by a macroH2A1-dependent silencing mechanism.

MeSH Terms
5' Untranslated Regions Animals DNA Methylation Endogenous Retroviruses/genetics Gene Expression Regulation, Viral Gene Silencing/physiology Genes, pol Histones/deficiency,genetics,physiology Leukemia Virus, Murine/genetics Liver/metabolism,virology Mice Mice, Inbred C57BL Mice, Knockout Nucleosomes/chemistry Proviruses/genetics Sequence Deletion Transcription, Genetic
Chemicals
5' Untranslated Regions Histones Nucleosomes macroH2A histone
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Changolkar Lakshmi N
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Singh Geetika
Pehrson John R
References (40)
40 references, click to expand
  1. Evolutionary conservation of histone macroH2A subtypes and domains.
    Nucleic Acids Res. 1998 Jun 15;26(12):2837-42 PMID: 9611225
  2. Cytosine methylation and the ecology of intragenomic parasites.
    Trends Genet. 1997 Aug;13(8):335-40 PMID: 9260521
  3. Transcription of IAP endogenous retroviruses is constrained by cytosine methylation.
    Nat Genet. 1998 Oct;20(2):116-7 PMID: 9771701
  4. Messenger RNAs encoding mouse histone macroH2A1 isoforms are expressed at similar levels in male and female cells and result from alternative splicing.
    Nucleic Acids Res. 1999 Sep 15;27(18):3685-9 PMID: 10471737
  5. An active murine transposon family pair: retrotransposition of "master" MusD copies and ETn trans-mobilization.
    Genome Res. 2004 Nov;14(11):2261-7 PMID: 15479948
  6. Dynamic relocation of epigenetic chromatin markers reveals an active role of constitutive heterochromatin in the transition from proliferation to quiescence.
    J Cell Sci. 2004 Dec 1;117(Pt 25):6153-62 PMID: 15564378
  7. Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA.
    Dev Cell. 2005 Jan;8(1):19-30 PMID: 15621527
  8. Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase.
    Proc Natl Acad Sci U S A. 2005 May 24;102(21):7635-40 PMID: 15897469
  9. Splicing regulates NAD metabolite binding to histone macroH2A.
    Nat Struct Mol Biol. 2005 Jul;12(7):624-5 PMID: 15965484
  10. Repbase Update, a database of eukaryotic repetitive elements.
    Cytogenet Genome Res. 2005;110(1-4):462-7 PMID: 16093699
  11. Mechanism of polymerase II transcription repression by the histone variant macroH2A.
    Mol Cell Biol. 2006 Feb;26(3):1156-64 PMID: 16428466
  12. macroH2A1 histone variants are depleted on active genes but concentrated on the inactive X chromosome.
    Mol Cell Biol. 2006 Jun;26(12):4410-20 PMID: 16738309
  13. Retroviral elements and their hosts: insertional mutagenesis in the mouse germ line.
    PLoS Genet. 2006 Jan;2(1):e2 PMID: 16440055
  14. Epigenetic determination of a cell-specific gene expression program by ATF-2 and the histone variant macroH2A.
    EMBO J. 2006 Oct 18;25(20):4843-53 PMID: 17036053
  15. Murine MusD retrotransposon: structure and molecular evolution of an "intracellularized" retrovirus.
    J Virol. 2007 Feb;81(4):1888-98 PMID: 17151128
  16. Developmental changes in histone macroH2A1-mediated gene regulation.
    Mol Cell Biol. 2007 Apr;27(7):2758-64 PMID: 17242180
  17. TRIM28 mediates primer binding site-targeted silencing of murine leukemia virus in embryonic cells.
    Cell. 2007 Oct 5;131(1):46-57 PMID: 17923087
  18. Gene silencing as a threat to the success of gene therapy.
    J Clin Invest. 2000 Feb;105(4):409-11 PMID: 10683368
  19. Histone macroH2A1 is concentrated in the inactive X chromosome of female preimplantation mouse embryos.
    Development. 2000 Jun;127(11):2283-9 PMID: 10804171
  20. Histone macroH2A1.2 is concentrated in the XY-body by the early pachytene stage of spermatogenesis.
    Exp Cell Res. 2000 Aug 1;258(2):254-60 PMID: 10896776
  21. Histone H2A variants and the inactive X chromosome: identification of a second macroH2A variant.
    Hum Mol Genet. 2001 May 1;10(10):1101-13 PMID: 11331621
  22. MACROH2A2, a new member of the MARCOH2A core histone family.
    J Biol Chem. 2001 Jun 15;276(24):21776-84 PMID: 11262398
  23. Induction of murine AIDS virus-related sequences after burn injury.
    J Surg Res. 2002 May 1;104(1):53-62 PMID: 11971678
  24. Injury-associated induction of two novel and replication-defective murine retroviral RNAs in the liver of mice.
    Virus Res. 2003 Jun;93(2):189-98 PMID: 12782367
  25. The crystal structure of AF1521 a protein from Archaeoglobus fulgidus with homology to the non-histone domain of macroH2A.
    J Mol Biol. 2003 Jul 11;330(3):503-11 PMID: 12842467
  26. Structure and expression of mobile ETnII retroelements and their coding-competent MusD relatives in the mouse.
    J Virol. 2003 Nov;77(21):11448-58 PMID: 14557630
  27. Structural characterization of macroH2A containing chromatin.
    Biochemistry. 2004 Feb 10;43(5):1352-9 PMID: 14756572
  28. Chromatin structure of endogenous retroviral genes and activation by an inhibitor of DNA methylation.
    Nature. 1981 Jul 23;292(5821):311-7 PMID: 6166864
  29. 5-Azacytidine induction of mouse endogenous type C virus and suppression of DNA methylation.
    Proc Natl Acad Sci U S A. 1981 Oct;78(10):6290-4 PMID: 6171816
  30. Treatment of mice with 5-azacytidine efficiently activates silent retroviral genomes in different tissues.
    Proc Natl Acad Sci U S A. 1985 Mar;82(5):1451-5 PMID: 2579397
  31. Chromosomal position or virus mutation permits retrovirus expression in embryonal carcinoma cells.
    Cell. 1986 Nov 7;47(3):391-9 PMID: 3768959
  32. Splice acceptor site for the env message of Moloney murine leukemia virus.
    J Virol. 1987 Jun;61(6):2038-41 PMID: 3573155
  33. Potential progenitor sequences of mink cell focus-forming (MCF) murine leukemia viruses: ecotropic, xenotropic, and MCF-related viral RNAs are detected concurrently in thymus tissues of AKR mice.
    J Virol. 1988 Feb;62(2):376-86 PMID: 2826802
  34. Severe immunodeficiency disease induced by a defective murine leukaemia virus.
    Nature. 1989 Apr 6;338(6215):505-8 PMID: 2538760
  35. Autonomous expression of RTVL-H endogenous retroviruslike elements in human cells.
    J Virol. 1990 May;64(5):2157-67 PMID: 2325205
  36. MacroH2A, a core histone containing a large nonhistone region.
    Science. 1992 Sep 4;257(5075):1398-400 PMID: 1529340
  37. Evidence for a functional subclass of the RTVL-H family of human endogenous retrovirus-like sequences.
    J Virol. 1993 Jun;67(6):2981-9 PMID: 8388483
  38. Frequent disruption of the Nf1 gene by a novel murine AIDS virus-related provirus in BXH-2 murine myeloid lymphomas.
    J Virol. 1995 Nov;69(11):7138-46 PMID: 7474134
  39. Developmental and tissue expression patterns of histone macroH2A1 subtypes.
    J Cell Biochem. 1997 Apr;65(1):107-13 PMID: 9138085
  40. Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals.
    Nature. 1998 Jun 11;393(6685):599-601 PMID: 9634239
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.01362-07
Published
2008-03-00
Epub
2008-00-14
Pages
2059-65
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2268408
Subset
IM
Grants
NIGMS NIH HHS · R01 GM049351 · United States
NIGMS NIH HHS · GM49351 · United States
External Links
PubMed source DOI: 10.1128/MCB.01362-07 PMC Full Text View journal details
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