KAP1 controls endogenous retroviruses in embryonic stem cells

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KAP1 controls endogenous retroviruses in embryonic stem cells. / Rowe, Helen M.; Jakobsson, Johan; Mesnard, Daniel; Rougemont, Jacques; Reynard, Severine; Aktas, Tugce; Maillard , Pierre V. ; Layard-Liesching, Hillary; Verp, Sonia; Marquis, Julien; Spitz, Francois; Constam, Daniel B.; Trono, Didier.

I: Nature, Vol. 463, 14.01.2010, s. 237-40.

Forskningsoutput: TidskriftsbidragLetter

Harvard

Rowe, HM, Jakobsson, J, Mesnard, D, Rougemont, J, Reynard, S, Aktas, T, Maillard , PV, Layard-Liesching, H, Verp, S, Marquis, J, Spitz, F, Constam, DB & Trono, D 2010, 'KAP1 controls endogenous retroviruses in embryonic stem cells', Nature, vol. 463, s. 237-40. https://doi.org/10.1038/nature08674

APA

Rowe, H. M., Jakobsson, J., Mesnard, D., Rougemont, J., Reynard, S., Aktas, T., ... Trono, D. (2010). KAP1 controls endogenous retroviruses in embryonic stem cells. Nature, 463, 237-40. https://doi.org/10.1038/nature08674

CBE

Rowe HM, Jakobsson J, Mesnard D, Rougemont J, Reynard S, Aktas T, Maillard PV, Layard-Liesching H, Verp S, Marquis J, Spitz F, Constam DB, Trono D. 2010. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature. 463:237-40. https://doi.org/10.1038/nature08674

MLA

Vancouver

Rowe HM, Jakobsson J, Mesnard D, Rougemont J, Reynard S, Aktas T et al. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature. 2010 jan 14;463:237-40. https://doi.org/10.1038/nature08674

Author

Rowe, Helen M. ; Jakobsson, Johan ; Mesnard, Daniel ; Rougemont, Jacques ; Reynard, Severine ; Aktas, Tugce ; Maillard , Pierre V. ; Layard-Liesching, Hillary ; Verp, Sonia ; Marquis, Julien ; Spitz, Francois ; Constam, Daniel B. ; Trono, Didier. / KAP1 controls endogenous retroviruses in embryonic stem cells. I: Nature. 2010 ; Vol. 463. s. 237-40.

RIS

TY - JOUR

T1 - KAP1 controls endogenous retroviruses in embryonic stem cells

AU - Rowe, Helen M.

AU - Jakobsson, Johan

AU - Mesnard, Daniel

AU - Rougemont, Jacques

AU - Reynard, Severine

AU - Aktas, Tugce

AU - Maillard , Pierre V.

AU - Layard-Liesching, Hillary

AU - Verp, Sonia

AU - Marquis, Julien

AU - Spitz, Francois

AU - Constam, Daniel B.

AU - Trono, Didier

PY - 2010/1/14

Y1 - 2010/1/14

N2 - More than forty per cent of the mammalian genome is derived from retroelements, of which about one-quarter are endogenous retroviruses (ERVs). Some are still active, notably in mice the highly polymorphic early transposon (ETn)/MusD and intracisternal A-type particles (IAP). ERVs are transcriptionally silenced during early embryogenesis by histone and DNA methylation (and reviewed in ref. 7), although the initiators of this process, which is essential to protect genome integrity, remain largely unknown. KAP1 (KRAB-associated protein 1, also known as tripartite motif-containing protein 28, TRIM28) represses genes by recruiting the histone methyltransferase SETDB1, heterochromatin protein 1 (HP1) and the NuRD histone deacetylase complex, but few of its physiological targets are known. Two lines of evidence suggest that KAP1-mediated repression could contribute to the control of ERVs: first, KAP1 can trigger permanent gene silencing during early embryogenesis, and second, a KAP1 complex silences the retrovirus murine leukaemia virus in embryonic cells. Consistent with this hypothesis, here we show that KAP1 deletion leads to a marked upregulation of a range of ERVs, in particular IAP elements, in mouse embryonic stem (ES) cells and in early embryos. We further demonstrate that KAP1 acts synergistically with DNA methylation to silence IAP elements, and that it is enriched at the 5' untranslated region (5'UTR) of IAP genomes, where KAP1 deletion leads to the loss of histone 3 lysine 9 trimethylation (H3K9me3), a hallmark of KAP1-mediated repression. Correspondingly, IAP 5'UTR sequences can impose in cis KAP1-dependent repression on a heterologous promoter in ES cells. Our results establish that KAP1 controls endogenous retroelements during early embryonic development.

AB - More than forty per cent of the mammalian genome is derived from retroelements, of which about one-quarter are endogenous retroviruses (ERVs). Some are still active, notably in mice the highly polymorphic early transposon (ETn)/MusD and intracisternal A-type particles (IAP). ERVs are transcriptionally silenced during early embryogenesis by histone and DNA methylation (and reviewed in ref. 7), although the initiators of this process, which is essential to protect genome integrity, remain largely unknown. KAP1 (KRAB-associated protein 1, also known as tripartite motif-containing protein 28, TRIM28) represses genes by recruiting the histone methyltransferase SETDB1, heterochromatin protein 1 (HP1) and the NuRD histone deacetylase complex, but few of its physiological targets are known. Two lines of evidence suggest that KAP1-mediated repression could contribute to the control of ERVs: first, KAP1 can trigger permanent gene silencing during early embryogenesis, and second, a KAP1 complex silences the retrovirus murine leukaemia virus in embryonic cells. Consistent with this hypothesis, here we show that KAP1 deletion leads to a marked upregulation of a range of ERVs, in particular IAP elements, in mouse embryonic stem (ES) cells and in early embryos. We further demonstrate that KAP1 acts synergistically with DNA methylation to silence IAP elements, and that it is enriched at the 5' untranslated region (5'UTR) of IAP genomes, where KAP1 deletion leads to the loss of histone 3 lysine 9 trimethylation (H3K9me3), a hallmark of KAP1-mediated repression. Correspondingly, IAP 5'UTR sequences can impose in cis KAP1-dependent repression on a heterologous promoter in ES cells. Our results establish that KAP1 controls endogenous retroelements during early embryonic development.

U2 - 10.1038/nature08674

DO - 10.1038/nature08674

M3 - Letter

VL - 463

SP - 237

EP - 240

JO - Nature

T2 - Nature

JF - Nature

SN - 0028-0836

ER -