Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance

Jessica Stringer, Samuel Forster, Zhipeng Qu, Lexie Ann Prokopuk, Moira Kathleen O'Bryan, David K. Gardner, Stefan White, David Louis Adelson, Patrick Stephen Western

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Defining the mechanisms that establish and regulate the transmission of epigenetic information from parent to offspring is critical for understanding disease heredity. Currently, the molecular pathways that regulate epigenetic information in the germline and its transmission to offspring are poorly understood.
Results: Here we provide evidence that Polycomb Repressive Complex 2 (PRC2) regulates paternal inheritance. Reduced PRC2 function in mice resulted in male sub-fertility and altered epigenetic and transcriptional control of retrotransposed elements in foetal male germ cells. Males with reduced PRC2 function produced offspring that over-expressed retrotransposed pseudogenes and had altered preimplantation embryo cleavage rates and cell cycle control.
Conclusion: This study reveals a novel role for the histone-modifying complex, PRC2, in paternal intergenerational transmission of epigenetic effects on offspring, with important implications for understanding disease inheritance.
Original languageEnglish
Article number104
Number of pages20
JournalBMC Biology
Volume16
DOIs
Publication statusPublished - 20 Sep 2018

Cite this

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title = "Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance",
abstract = "Background: Defining the mechanisms that establish and regulate the transmission of epigenetic information from parent to offspring is critical for understanding disease heredity. Currently, the molecular pathways that regulate epigenetic information in the germline and its transmission to offspring are poorly understood.Results: Here we provide evidence that Polycomb Repressive Complex 2 (PRC2) regulates paternal inheritance. Reduced PRC2 function in mice resulted in male sub-fertility and altered epigenetic and transcriptional control of retrotransposed elements in foetal male germ cells. Males with reduced PRC2 function produced offspring that over-expressed retrotransposed pseudogenes and had altered preimplantation embryo cleavage rates and cell cycle control.Conclusion: This study reveals a novel role for the histone-modifying complex, PRC2, in paternal intergenerational transmission of epigenetic effects on offspring, with important implications for understanding disease inheritance.",
author = "Jessica Stringer and Samuel Forster and Zhipeng Qu and Prokopuk, {Lexie Ann} and O'Bryan, {Moira Kathleen} and Gardner, {David K.} and Stefan White and Adelson, {David Louis} and Western, {Patrick Stephen}",
year = "2018",
month = "9",
day = "20",
doi = "10.1186/s12915-018-0569-5",
language = "English",
volume = "16",
journal = "BMC Biology",
issn = "1741-7007",
publisher = "Springer-Verlag London Ltd.",

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Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance. / Stringer, Jessica; Forster, Samuel; Qu, Zhipeng; Prokopuk, Lexie Ann; O'Bryan, Moira Kathleen; Gardner, David K.; White, Stefan; Adelson, David Louis; Western, Patrick Stephen.

In: BMC Biology, Vol. 16, 104, 20.09.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance

AU - Stringer, Jessica

AU - Forster, Samuel

AU - Qu, Zhipeng

AU - Prokopuk, Lexie Ann

AU - O'Bryan, Moira Kathleen

AU - Gardner, David K.

AU - White, Stefan

AU - Adelson, David Louis

AU - Western, Patrick Stephen

PY - 2018/9/20

Y1 - 2018/9/20

N2 - Background: Defining the mechanisms that establish and regulate the transmission of epigenetic information from parent to offspring is critical for understanding disease heredity. Currently, the molecular pathways that regulate epigenetic information in the germline and its transmission to offspring are poorly understood.Results: Here we provide evidence that Polycomb Repressive Complex 2 (PRC2) regulates paternal inheritance. Reduced PRC2 function in mice resulted in male sub-fertility and altered epigenetic and transcriptional control of retrotransposed elements in foetal male germ cells. Males with reduced PRC2 function produced offspring that over-expressed retrotransposed pseudogenes and had altered preimplantation embryo cleavage rates and cell cycle control.Conclusion: This study reveals a novel role for the histone-modifying complex, PRC2, in paternal intergenerational transmission of epigenetic effects on offspring, with important implications for understanding disease inheritance.

AB - Background: Defining the mechanisms that establish and regulate the transmission of epigenetic information from parent to offspring is critical for understanding disease heredity. Currently, the molecular pathways that regulate epigenetic information in the germline and its transmission to offspring are poorly understood.Results: Here we provide evidence that Polycomb Repressive Complex 2 (PRC2) regulates paternal inheritance. Reduced PRC2 function in mice resulted in male sub-fertility and altered epigenetic and transcriptional control of retrotransposed elements in foetal male germ cells. Males with reduced PRC2 function produced offspring that over-expressed retrotransposed pseudogenes and had altered preimplantation embryo cleavage rates and cell cycle control.Conclusion: This study reveals a novel role for the histone-modifying complex, PRC2, in paternal intergenerational transmission of epigenetic effects on offspring, with important implications for understanding disease inheritance.

U2 - 10.1186/s12915-018-0569-5

DO - 10.1186/s12915-018-0569-5

M3 - Article

VL - 16

JO - BMC Biology

JF - BMC Biology

SN - 1741-7007

M1 - 104

ER -