LINE-1 silencing by retinoblastoma proteins is effected through the nucleosomal and remodeling deacetylase multiprotein complex

BMC Cancer
Diego E Montoya-DurangoKenneth S Ramos

Abstract

Long Interspersed Nuclear Element-1 (L1) is an oncogenic mammalian retroelement silenced early in development via tightly controlled epigenetic mechanisms. We have previously shown that the regulatory region of human and murine L1s interact with retinoblastoma (RB) proteins to effect retroelement silencing. The present studies were conducted to identify the corepressor complex responsible for RB-mediated silencing of L1. Chromatin immunoprecipitation and silencing RNA technology were used to identify the repressor complex that silences L1 in human and murine cells. Components of the Nucleosomal and Remodeling Deacetylase (NuRD) multiprotein complex specifically enriched the L1 5'-untranslated DNA sequence in human and murine cells. Genetic ablation of RB proteins in murine cells destabilized interactions within the NuRD macromolecular complex and mediated nuclear rearrangement of Mi2-β, an ATP-dependent helicase subunit with nucleosome remodeling activity. Depletion of Mi2-β, RbAP46 and HDAC2 reduced the repressor activity of the NuRD complex and reactivated a synthetic L1 reporter in human cells. Epigenetic reactivation of L1 in RB-null cells by DNA damage was markedly enhanced compared to wild type cells. RB proteins stabiliz...Continue Reading

References

Sep 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·J A HuralM A Brown
Apr 26, 2003·The Journal of Biological Chemistry·Kim P Lu, Kenneth S Ramos
Jun 11, 2004·Immunity·Christine J WilliamsKatia Georgopoulos
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Oct 2, 2007·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Ivo TenengKenneth S Ramos
May 12, 2009·Mutation Research·Diego E Montoya-DurangoKenneth S Ramos
Mar 11, 2010·Nucleic Acids Research·Victoria P BelancioPrescott Deininger
Nov 19, 2010·Nature·Alysson R MuotriFred H Gage
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Jun 30, 2012·Science·Eunjung LeeUNKNOWN Cancer Genome Atlas Research Network
Oct 17, 2012·Molecular and Cellular Biology·Julita RamírezJames Hagman
May 8, 2013·Molecular Oncology·Pasano BojangKenneth S Ramos

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Citations

May 19, 2017·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Somnath PaulPritha Bhattacharjee
Aug 16, 2016·Mobile DNA·John L Goodier
Apr 26, 2018·Nature Reviews. Cancer·Frederick A DickNicholas J Dyson
Aug 7, 2018·F1000Research·Kristie N RamosKenneth S Ramos
Oct 10, 2021·FEBS Letters·Camille Ravel-GodreuilJulia Fuchs

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Methods Mentioned

BETA
PCR
immunoprecipitation
transfection
acetylation

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