title: Maternally provided LSD1/KDM1A enables the maternal-to-zygotic transition and prevents defects that manifest postnatally.
abstract: Somatic cell nuclear transfer has established that the oocyte contains maternal factors with epigenetic reprogramming capacity. Yet the identity and function of these maternal factors during the gamete to embryo transition remains poorly understood. In C. elegans, LSD1/KDM1A enables this transition by removing H3K4me2 and preventing the transgenerational inheritance of transcription patterns. Here we show that loss of maternal LSD1/KDM1A in mice results in embryonic arrest at the 1-2 cell stage, with arrested embryos failing to undergo the maternal-to-zygotic transition. This suggests that LSD1/KDM1A maternal reprogramming is conserved. Moreover, partial loss of maternal LSD1/KDM1A results in striking phenotypes weeks after fertilization; including perinatal lethality and abnormal behavior in surviving adults. These maternal effect hypomorphic phenotypes are associated with alterations in DNA methylation and expression at imprinted genes. These results establish a novel mammalian paradigm where defects in early epigenetic reprogramming can lead to defects that manifest later in development.
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, United States.|Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, United States.
authors.forename: Jadiel A
authors.initials: JA
authors.lastname: Wasson
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, United States.
authors.forename: Ashley K
authors.initials: AK
authors.lastname: Simon
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, United States.|Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, United States.
authors.forename: Dexter A
authors.initials: DA
authors.lastname: Myrick
authors.affiliation: The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
authors.forename: Gernot
authors.initials: G
authors.lastname: Wolf
authors.affiliation: Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, United States.|Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Shawn
authors.initials: S
authors.lastname: Driscoll
authors.affiliation: Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, United States.|Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Pfaff
authors.affiliation: The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
authors.forename: Todd S
authors.initials: TS
authors.lastname: Macfarlan
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, United States.
authors.forename: David J
authors.identifier: http://orcid.org/0000-0002-3040-1142
authors.initials: DJ
authors.lastname: Katz
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019175:DNA Methylation; D047108:Embryonic Development; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D056466:Histone Demethylases / Q000378:metabolism*; D051379:Mice; D009865:Oocytes / Q000201:enzymology* / Q000502:physiology*; D015053:Zygote / Q000201:enzymology* / Q000502:physiology*
chemical_list: D056466:Histone Demethylases; C504076:KDM1a protein, mouse
keywords: KDM1a; LSD1; MZT; developmental biology; epigenetics; genomic imprinting; maternal effect; mouse; stem cells
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