Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation

Upon fertilization, the highly specialised sperm and oocyte genomes are remodelled to confer totipotency. The mechanisms of the dramatic reprogramming events that occur have remained unknown, and presumed roles of histone modifying enzymes are just starting to be elucidated. Here, we explore the fun...

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Main Authors: Katia Ancelin, Laurène Syx, Maud Borensztein, Noémie Ranisavljevic, Ivaylo Vassilev, Luis Briseño-Roa, Tao Liu, Eric Metzger, Nicolas Servant, Emmanuel Barillot, Chong-Jian Chen, Roland Schüle, Edith Heard
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2016-02-01
Series:eLife
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Online Access:https://elifesciences.org/articles/08851
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author Katia Ancelin
Laurène Syx
Maud Borensztein
Noémie Ranisavljevic
Ivaylo Vassilev
Luis Briseño-Roa
Tao Liu
Eric Metzger
Nicolas Servant
Emmanuel Barillot
Chong-Jian Chen
Roland Schüle
Edith Heard
author_facet Katia Ancelin
Laurène Syx
Maud Borensztein
Noémie Ranisavljevic
Ivaylo Vassilev
Luis Briseño-Roa
Tao Liu
Eric Metzger
Nicolas Servant
Emmanuel Barillot
Chong-Jian Chen
Roland Schüle
Edith Heard
author_sort Katia Ancelin
collection DOAJ
description Upon fertilization, the highly specialised sperm and oocyte genomes are remodelled to confer totipotency. The mechanisms of the dramatic reprogramming events that occur have remained unknown, and presumed roles of histone modifying enzymes are just starting to be elucidated. Here, we explore the function of the oocyte-inherited pool of a histone H3K4 and K9 demethylase, LSD1/KDM1A during early mouse development. KDM1A deficiency results in developmental arrest by the two-cell stage, accompanied by dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns. At the transcriptional level, the switch of the maternal-to-zygotic transition fails to be induced properly and LINE-1 retrotransposons are not properly silenced. We propose that KDM1A plays critical roles in establishing the correct epigenetic landscape of the zygote upon fertilization, in preserving genome integrity and in initiating new patterns of genome expression that drive early mouse development.
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spelling doaj.art-101668d09c744ddfb12d6a5d6d258a702022-12-22T03:52:41ZengeLife Sciences Publications LtdeLife2050-084X2016-02-01510.7554/eLife.08851Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activationKatia Ancelin0Laurène Syx1Maud Borensztein2Noémie Ranisavljevic3Ivaylo Vassilev4Luis Briseño-Roa5Tao Liu6Eric Metzger7Nicolas Servant8Emmanuel Barillot9Chong-Jian Chen10Roland Schüle11Edith Heard12https://orcid.org/0000-0001-8052-7117Institut Curie, Paris, France; Genetics and Developmental Biology Unit, INSERM, Paris, FranceInstitut Curie, Paris, France; Bioinformatics and Computational Systems Biology of Cancer, INSERM, Paris, France; Mines ParisTech, Fontainebleau, FranceInstitut Curie, Paris, France; Genetics and Developmental Biology Unit, INSERM, Paris, FranceInstitut Curie, Paris, France; Genetics and Developmental Biology Unit, INSERM, Paris, FranceInstitut Curie, Paris, France; Bioinformatics and Computational Systems Biology of Cancer, INSERM, Paris, France; Mines ParisTech, Fontainebleau, FranceHigh Fidelity Biology, Paris, FranceAnnoroad Gene Technology Co., Ltd, Beijing, ChinaUrologische Klinik und Zentrale Klinische Forschung, Freiburg, GermanyInstitut Curie, Paris, France; Bioinformatics and Computational Systems Biology of Cancer, INSERM, Paris, France; Mines ParisTech, Fontainebleau, FranceInstitut Curie, Paris, France; Bioinformatics and Computational Systems Biology of Cancer, INSERM, Paris, France; Mines ParisTech, Fontainebleau, FranceAnnoroad Gene Technology Co., Ltd, Beijing, ChinaUrologische Klinik und Zentrale Klinische Forschung, Freiburg, GermanyInstitut Curie, Paris, France; Genetics and Developmental Biology Unit, INSERM, Paris, FranceUpon fertilization, the highly specialised sperm and oocyte genomes are remodelled to confer totipotency. The mechanisms of the dramatic reprogramming events that occur have remained unknown, and presumed roles of histone modifying enzymes are just starting to be elucidated. Here, we explore the function of the oocyte-inherited pool of a histone H3K4 and K9 demethylase, LSD1/KDM1A during early mouse development. KDM1A deficiency results in developmental arrest by the two-cell stage, accompanied by dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns. At the transcriptional level, the switch of the maternal-to-zygotic transition fails to be induced properly and LINE-1 retrotransposons are not properly silenced. We propose that KDM1A plays critical roles in establishing the correct epigenetic landscape of the zygote upon fertilization, in preserving genome integrity and in initiating new patterns of genome expression that drive early mouse development.https://elifesciences.org/articles/08851epigenetic reprogramminghistone demethylationpreimplantation developmentlysine methylationtranscription regulationretrotransposons
spellingShingle Katia Ancelin
Laurène Syx
Maud Borensztein
Noémie Ranisavljevic
Ivaylo Vassilev
Luis Briseño-Roa
Tao Liu
Eric Metzger
Nicolas Servant
Emmanuel Barillot
Chong-Jian Chen
Roland Schüle
Edith Heard
Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation
eLife
epigenetic reprogramming
histone demethylation
preimplantation development
lysine methylation
transcription regulation
retrotransposons
title Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation
title_full Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation
title_fullStr Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation
title_full_unstemmed Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation
title_short Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation
title_sort maternal lsd1 kdm1a is an essential regulator of chromatin and transcription landscapes during zygotic genome activation
topic epigenetic reprogramming
histone demethylation
preimplantation development
lysine methylation
transcription regulation
retrotransposons
url https://elifesciences.org/articles/08851
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