title: Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation.
abstract: 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.
authors.affiliation: Institut Curie, Paris, France.|Genetics and Developmental Biology Unit, INSERM, Paris, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Ancelin
authors.affiliation: Institut Curie, Paris, France.|Bioinformatics and Computational Systems Biology of Cancer, INSERM, Paris, France.|Mines ParisTech, Fontainebleau, France.
authors.forename: Laurène
authors.initials: L
authors.lastname: Syx
authors.affiliation: Institut Curie, Paris, France.|Genetics and Developmental Biology Unit, INSERM, Paris, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Borensztein
authors.affiliation: Institut Curie, Paris, France.|Genetics and Developmental Biology Unit, INSERM, Paris, France.
authors.forename: Noémie
authors.initials: N
authors.lastname: Ranisavljevic
authors.affiliation: Institut Curie, Paris, France.|Bioinformatics and Computational Systems Biology of Cancer, INSERM, Paris, France.|Mines ParisTech, Fontainebleau, France.
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Vassilev
authors.affiliation: High Fidelity Biology, Paris, France.
authors.forename: Luis
authors.initials: L
authors.lastname: Briseño-Roa
authors.affiliation: Annoroad Gene Technology Co., Ltd, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Freiburg, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Metzger
authors.affiliation: Institut Curie, Paris, France.|Bioinformatics and Computational Systems Biology of Cancer, INSERM, Paris, France.|Mines ParisTech, Fontainebleau, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Servant
authors.affiliation: Institut Curie, Paris, France.|Bioinformatics and Computational Systems Biology of Cancer, INSERM, Paris, France.|Mines ParisTech, Fontainebleau, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barillot
authors.affiliation: Annoroad Gene Technology Co., Ltd, Beijing, China.
authors.forename: Chong-Jian
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Freiburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Schüle
authors.affiliation: Institut Curie, Paris, France.|Genetics and Developmental Biology Unit, INSERM, Paris, France.
authors.forename: Edith
authors.identifier: http://orcid.org/0000-0001-8052-7117
authors.initials: E
authors.lastname: Heard
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D047108:Embryonic Development; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D056466:Histone Demethylases / Q000378:metabolism*; D051379:Mice; D009865:Oocytes / Q000201:enzymology / Q000502:physiology; D014158:Transcription, Genetic; D015053:Zygote / Q000201:enzymology* / Q000502:physiology*
chemical_list: D002843:Chromatin; D056466:Histone Demethylases; C504076:KDM1a protein, mouse
keywords: chromosomes; developmental biology; epigenetic reprogramming; genes; histone demethylation; lysine methylation; mouse; preimplantation development; retrotransposons; stem cells; transcription regulation
references.citation: J Microsc. 2006 Dec;224(Pt 3):213-32
references.pmid: 17210054
references.citation: Bioinformatics. 2015 Jan 15;31(2):166-9
references.pmid: 25260700
references.citation: Nat Chem Biol. 2012 May;8(5):417-27
references.pmid: 22510649
references.citation: J Cell Sci. 1997 May;110 ( Pt 10):1147-58
references.pmid: 9191039
references.citation: Mol Cell. 2015 Mar 19;57(6):957-70
references.pmid: 25684206
references.citation: Nat Genet. 2009 Jan;41(1):125-9
references.pmid: 19098913
references.citation: Development. 1997 Nov;124(22):4615-25
references.pmid: 9409678
references.citation: BMC Dev Biol. 2004 Sep 21;4:12
references.pmid: 15383155
references.citation: Curr Biol. 2003 Jul 1;13(13):1116-21
references.pmid: 12842010
references.citation: EMBO J. 1982;1(6):681-6
references.pmid: 7188357
references.citation: Dev Biol. 2008 Jul 1;319(1):110-20
references.pmid: 18501342
references.citation: Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
references.pmid: 12184808
references.citation: Genes Dev. 2013 Dec 15;27(24):2736-48
references.pmid: 24352427
references.citation: Genes Dev. 2009 Jun 1;23(11):1303-12
references.pmid: 19487571
references.citation: Philos Trans R Soc Lond B Biol Sci. 2013 Jan 5;368(1609):20110330
references.pmid: 23166394
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5198-203
references.pmid: 19273861
references.citation: Dev Cell. 2004 Oct;7(4):597-606
references.pmid: 15469847
references.citation: Genes Dev. 2014 Mar 1;28(5):463-78
references.pmid: 24589776
references.citation: PLoS Biol. 2010;8(8). pii: e1000453. doi: 10.1371/journal.pbio.1000453
references.pmid: 20808952
references.citation: Genome Biol. 2010;11(10):R106
references.pmid: 20979621
references.citation: Bioinformatics. 2009 May 1;25(9):1105-11
references.pmid: 19289445
references.citation: Nature. 2013 Aug 29;500(7464):593-7
references.pmid: 23892778
references.citation: Bioinformatics. 2009 Jan 15;25(2):288-9
references.pmid: 19033274
references.citation: Science. 2013 Sep 6;341(6150):1110-2
references.pmid: 24009393
references.citation: Cell. 2009 Apr 17;137(2):308-20
references.pmid: 19379696
references.citation: Development. 2010 Mar;137(6):859-70
references.pmid: 20179092
references.citation: Nat Struct Mol Biol. 2013 Mar;20(3):332-8
references.pmid: 23353788
references.citation: Genesis. 2000 Feb;26(2):110-2
references.pmid: 10686600
references.citation: Dev Cell. 2004 Jan;6(1):117-31
references.pmid: 14723852
references.citation: Nature. 2005 Sep 15;437(7057):436-9
references.pmid: 16079795
references.citation: Cell. 2014 Nov 6;159(4):884-95
references.pmid: 25417163
references.citation: Int J Dev Biol. 2006;50(5):455-61
references.pmid: 16586346
references.citation: Nature. 2007 Apr 19;446(7138):882-7
references.pmid: 17392792
references.citation: In Vitro Cell Dev Biol Anim. 2014 Aug;50(7):603-13
references.pmid: 24619213
references.citation: EMBO J. 2005 Feb 23;24(4):800-12
references.pmid: 15678104
references.citation: Science. 2012 Mar 23;335(6075):1499-502
references.pmid: 22442485
references.citation: Nucleic Acids Res. 2015 Apr 20;43(7):e47
references.pmid: 25605792
references.citation: Mol Cell Biol. 2001 Jul;21(13):4330-6
references.pmid: 11390661
references.citation: Cell. 2010 Jun 11;141(6):956-69
references.pmid: 20550932
references.citation: Nat Rev Genet. 2012 May;13(5):343-57
references.pmid: 22473383
references.citation: Cell. 2004 Dec 29;119(7):941-53
references.pmid: 15620353
references.citation: Nat Cell Biol. 2010 Sep;12(9):853-62
references.pmid: 20676102
references.citation: Mol Cell Biol. 2010 Oct;30(20):4851-63
references.pmid: 20713442
references.citation: Genome Biol. 2009;10(3):R25
references.pmid: 19261174
references.citation: Dev Cell. 2010 Oct 19;19(4):625-38
references.pmid: 20951352
references.citation: Nat Genet. 2008 Apr;40(4):411-20
references.pmid: 18311137
references.citation: Biol Reprod. 2001 Jun;64(6):1713-21
references.pmid: 11369600
references.citation: Curr Biol. 2007 May 1;17(9):808-12
references.pmid: 17462898
references.citation: Genes Dev. 2011 Mar 15;25(6):594-607
references.pmid: 21357675
references.citation: BMC Dev Biol. 2007;7:14
references.pmid: 17341302
references.citation: Genes Dev. 2012 May 1;26(9):920-32
references.pmid: 22499591
references.citation: Development. 2006 Apr;133(8):1423-32
references.pmid: 16540515
references.citation: Int J Dev Biol. 2002 May;46(3):317-20
references.pmid: 12068953
references.citation: Mol Cell. 2012 Nov 30;48(4):491-507
references.pmid: 23200123
references.citation: Nat Commun. 2015;6:10116
references.pmid: 26626423
references.citation: Gene Expr Patterns. 2012 May-Jun;12(5-6):213-8
references.pmid: 22504302
references.citation: J Biol Chem. 1995 Sep 22;270(38):22077-80
references.pmid: 7673179
references.citation: Development. 2003 Sep;130(18):4235-48
references.pmid: 12900441
references.citation: Dev Biol. 2005 Apr 1;280(1):225-36
references.pmid: 15766761
references.citation: Curr Biol. 1997 Feb 1;7(2):148-51
references.pmid: 9016703
references.citation: Nature. 2009 Sep 17;461(7262):415-8
references.pmid: 19727073
references.citation: Nat Protoc. 2010 Mar;5(3):516-35
references.pmid: 20203668
references.citation: Trends Biochem Sci. 2012 Apr;37(4):127-33
references.pmid: 22178137
references.citation: Brief Funct Genomics. 2010 Dec;9(5-6):444-54
references.pmid: 21186177
references.citation: Nat Commun. 2014;5:3174
references.pmid: 24448552