Finn Skou Pedersen

The KRAB zinc finger protein ZFP809 is required to initiate epigenetic silencing of endogenous retroviruses

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The KRAB zinc finger protein ZFP809 is required to initiate epigenetic silencing of endogenous retroviruses. / Wolf, Gernot; Yang, Peng; Füchtbauer, Annette C; Füchtbauer, Ernst-Martin; Silva, Andreia M; Park, Chungoo; Wu, Warren; Nielsen, Anders Lade; Pedersen, Finn S; Macfarlan, Todd S.

In: Genes & Development, Vol. 29, No. 5, 01.03.2015, p. 538-54.

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Wolf, Gernot ; Yang, Peng ; Füchtbauer, Annette C ; Füchtbauer, Ernst-Martin ; Silva, Andreia M ; Park, Chungoo ; Wu, Warren ; Nielsen, Anders Lade ; Pedersen, Finn S ; Macfarlan, Todd S. / The KRAB zinc finger protein ZFP809 is required to initiate epigenetic silencing of endogenous retroviruses. In: Genes & Development. 2015 ; Vol. 29, No. 5. pp. 538-54.

Bibtex

@article{2c7714423d66497bb655adf5f62d1389,
title = "The KRAB zinc finger protein ZFP809 is required to initiate epigenetic silencing of endogenous retroviruses",
abstract = "Retroviruses have been invading mammalian germlines for millions of years, accumulating in the form of endogenous retroviruses (ERVs) that account for nearly one-tenth of the mouse and human genomes. ERVs are epigenetically silenced during development, yet the cellular factors recognizing ERVs in a sequence-specific manner remain elusive. Here we demonstrate that ZFP809, a member of the Kr{\"u}ppel-associated box zinc finger protein (KRAB-ZFP) family, initiates the silencing of ERVs in a sequence-specific manner via recruitment of heterochromatin-inducing complexes. ZFP809 knockout mice display highly elevated levels of ZFP809-targeted ERVs in somatic tissues. ERV reactivation is accompanied by an epigenetic shift from repressive to active histone modifications but only slight destabilization of DNA methylation. Importantly, using conditional alleles and rescue experiments, we demonstrate that ZFP809 is required to initiate ERV silencing during embryonic development but becomes largely dispensable in somatic tissues. Finally, we show that the DNA-binding specificity of ZFP809 is evolutionarily conserved in the Muroidea superfamily of rodents and predates the endogenization of retroviruses presently targeted by ZFP809 in Mus musculus. In sum, these data provide compelling evidence that ZFP809 evolved to recognize foreign DNA and establish histone modification-based epigenetic silencing of ERVs.",
author = "Gernot Wolf and Peng Yang and F{\"u}chtbauer, {Annette C} and Ernst-Martin F{\"u}chtbauer and Silva, {Andreia M} and Chungoo Park and Warren Wu and Nielsen, {Anders Lade} and Pedersen, {Finn S} and Macfarlan, {Todd S}",
note = "Published by Cold Spring Harbor Laboratory Press.",
year = "2015",
month = mar,
day = "1",
doi = "10.1101/gad.252767.114",
language = "English",
volume = "29",
pages = "538--54",
journal = "Genes & Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "5",

}

RIS

TY - JOUR

T1 - The KRAB zinc finger protein ZFP809 is required to initiate epigenetic silencing of endogenous retroviruses

AU - Wolf, Gernot

AU - Yang, Peng

AU - Füchtbauer, Annette C

AU - Füchtbauer, Ernst-Martin

AU - Silva, Andreia M

AU - Park, Chungoo

AU - Wu, Warren

AU - Nielsen, Anders Lade

AU - Pedersen, Finn S

AU - Macfarlan, Todd S

N1 - Published by Cold Spring Harbor Laboratory Press.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Retroviruses have been invading mammalian germlines for millions of years, accumulating in the form of endogenous retroviruses (ERVs) that account for nearly one-tenth of the mouse and human genomes. ERVs are epigenetically silenced during development, yet the cellular factors recognizing ERVs in a sequence-specific manner remain elusive. Here we demonstrate that ZFP809, a member of the Krüppel-associated box zinc finger protein (KRAB-ZFP) family, initiates the silencing of ERVs in a sequence-specific manner via recruitment of heterochromatin-inducing complexes. ZFP809 knockout mice display highly elevated levels of ZFP809-targeted ERVs in somatic tissues. ERV reactivation is accompanied by an epigenetic shift from repressive to active histone modifications but only slight destabilization of DNA methylation. Importantly, using conditional alleles and rescue experiments, we demonstrate that ZFP809 is required to initiate ERV silencing during embryonic development but becomes largely dispensable in somatic tissues. Finally, we show that the DNA-binding specificity of ZFP809 is evolutionarily conserved in the Muroidea superfamily of rodents and predates the endogenization of retroviruses presently targeted by ZFP809 in Mus musculus. In sum, these data provide compelling evidence that ZFP809 evolved to recognize foreign DNA and establish histone modification-based epigenetic silencing of ERVs.

AB - Retroviruses have been invading mammalian germlines for millions of years, accumulating in the form of endogenous retroviruses (ERVs) that account for nearly one-tenth of the mouse and human genomes. ERVs are epigenetically silenced during development, yet the cellular factors recognizing ERVs in a sequence-specific manner remain elusive. Here we demonstrate that ZFP809, a member of the Krüppel-associated box zinc finger protein (KRAB-ZFP) family, initiates the silencing of ERVs in a sequence-specific manner via recruitment of heterochromatin-inducing complexes. ZFP809 knockout mice display highly elevated levels of ZFP809-targeted ERVs in somatic tissues. ERV reactivation is accompanied by an epigenetic shift from repressive to active histone modifications but only slight destabilization of DNA methylation. Importantly, using conditional alleles and rescue experiments, we demonstrate that ZFP809 is required to initiate ERV silencing during embryonic development but becomes largely dispensable in somatic tissues. Finally, we show that the DNA-binding specificity of ZFP809 is evolutionarily conserved in the Muroidea superfamily of rodents and predates the endogenization of retroviruses presently targeted by ZFP809 in Mus musculus. In sum, these data provide compelling evidence that ZFP809 evolved to recognize foreign DNA and establish histone modification-based epigenetic silencing of ERVs.

U2 - 10.1101/gad.252767.114

DO - 10.1101/gad.252767.114

M3 - Journal article

C2 - 25737282

VL - 29

SP - 538

EP - 554

JO - Genes & Development

JF - Genes & Development

SN - 0890-9369

IS - 5

ER -