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 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. DOI: http://dx.doi.org/10.7554/eLife.08851.001

• Publication year

  2016

• Venue

  eLife

• Publication date

  2016-02-02

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.7554/eLife.08851PMID 26836306PMCID 4829419
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• limma powers differential expression analyses for RNA-sequencing and microarray studies

  2015influential reference
• LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice

  2015cited by this paper
• A specific LSD1/KDM1A isoform regulates neuronal differentiation through H3K9 demethylation.

  2015cited by this paper
• HTSeq—a Python framework to work with high-throughput sequencing data

  2014influential reference
• Embryonic development following somatic cell nuclear transfer impeded by persisting histone methylation.

  2014cited by this paper
• Dynamic patterns of histone H3 lysine 4 methyltransferases and demethylases during mouse preimplantation development

  2014cited by this paper
• Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells

  2014cited by this paper
• L1 retrotransposition

  2014cited by this paper
• The Gpr1/Zdbf2 locus provides new paradigms for transient and dynamic genomic imprinting in mammals

  2014cited by this paper
• Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA

  2013influential reference
• Reprogramming DNA methylation in the mammalian life cycle: building and breaking epigenetic barriers

  2013cited by this paper
• Inferring the choreography of parental genomes during fertilization from ultralarge-scale whole-transcriptome analysis

  2013influential reference
• Single-Cell DNA-Methylation Analysis Reveals Epigenetic Chimerism in Preimplantation Embryos

  2013cited by this paper
• Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing

  2013cited by this paper
• Silencing of endogenous retroviruses: when and why do histone marks predominate?

  2012cited by this paper
• Histone methylation: a dynamic mark in health, disease and inheritance

  2012cited by this paper
• Trim28 Is Required for Epigenetic Stability During Mouse Oocyte to Embryo Transition

  2012cited by this paper
• Polycomb function during oogenesis is required for mouse embryonic development.

  2012cited by this paper
• Dynamics of Setdb1 expression in early mouse development.

  2012influential reference
• Histone lysine methylation dynamics: establishment, regulation, and biological impact.

  2012influential reference
• Chromatin as an expansive canvas for chemical biology.

  2012cited by this paper
• Endogenous retroviruses and neighboring genes are coordinately repressed by LSD1/KDM1A.

  2011influential reference
• Integrating diverse genomic data using gene sets

  2011influential reference
• Epigenetic reprogramming and development: a unique heterochromatin organization in the preimplantation mouse embryo.

  2010influential reference
• Differential expression analysis for sequence count data

  2010cited by this paper
• LINE-1 activity in facultative heterochromatin formation during X chromosome inactivation.

  2010cited by this paper
• Lysine-Specific Demethylase 1 Regulates the Embryonic Transcriptome and CoREST Stability

  2010cited by this paper
• A strand-specific burst in transcription of pericentric satellites is required for chromocenter formation and early mouse development.

  2010cited by this paper
• Maternal control of early mouse development

  2010cited by this paper
• RNA-Seq analysis to capture the transcriptome landscape of a single cell

  2010cited by this paper
• Heterochromatin formation in the mouse embryo requires critical residues of the histone variant H3.3

  2010cited by this paper
• MLL2 Is Required in Oocytes for Bulk Histone 3 Lysine 4 Trimethylation and Transcriptional Silencing

  2010cited by this paper
• Searching for SNPs with cloud computing

  2009cited by this paper
• A C. elegans LSD1 demethylase contributes to germline immortality by reprogramming epigenetic memory.

  2009cited by this paper
• Ultrafast and memory-efficient alignment of short DNA sequences to the human genome

  2009cited by this paper
• Dynamic changes in paternal X-chromosome activity during imprinted X-chromosome inactivation in mice

  2009cited by this paper
• The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation

  2009cited by this paper
• TopHat: discovering splice junctions with RNA-Seq

  2009cited by this paper
• KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints

  2009cited by this paper
• L1 retrotransposition occurs mainly in embryogenesis and creates somatic mosaicism.

  2009cited by this paper
• Histone deacetylase 1 (HDAC1) regulates histone acetylation, development, and gene expression in preimplantation mouse embryos.

  2008cited by this paper
• PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos

  2008influential reference
• AmiGO: online access to ontology and annotation data

  2008influential reference
• Quantitative evaluation and selection of reference genes in mouse oocytes and embryos cultured in vivo and in vitro

  2007cited by this paper
• Opposing LSD1 complexes function in developmental gene activation and repression programmes

  2007cited by this paper
• Mutation of Drosophila Lsd1 disrupts H3-K4 methylation, resulting in tissue-specific defects during development.

  2007cited by this paper
• Multiple epigenetic maintenance factors implicated by the loss of Mll2 in mouse development

  2006cited by this paper
• Dynamic distribution of the replacement histone variant H3.3 in the mouse oocyte and preimplantation embryos.

  2006cited by this paper
• A guided tour into subcellular colocalization analysis in light microscopy

  2006cited by this paper
• Dynamic chromatin modifications characterise the first cell cycle in mouse embryos.

  2005cited by this paper
• Changes in gravitational force affect gene expression in developing organ systems at different developmental times

  2005influential reference
• The profile of repeat‐associated histone lysine methylation states in the mouse epigenome

  2005influential reference
• LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription

  2005influential reference
• Differential dynamics of histone H3 methylation at positions K4 and K9 in the mouse zygote

  2004cited by this paper
• Histone demethylation mediated by the nuclear amine oxidase homolog LSD1.

  2004cited by this paper
• Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos.

  2004cited by this paper
• Dynamics of global gene expression changes during mouse preimplantation development.

  2004cited by this paper
• Epigenetic marking correlates with developmental potential in cloned bovine preimplantation embryos.

  2003cited by this paper
• Consequences of the depletion of zygotic and embryonic enhancer of zeste 2 during preimplantation mouse development

  2003cited by this paper
• Histone methylation defines epigenetic asymmetry in the mouse zygote.

  2002cited by this paper
• Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes

  2002cited by this paper
• The Polycomb-Group GeneEzh2 Is Required for Early Mouse Development

  2001cited by this paper
• Regulation of Zygotic Gene Activation in the Preimplantation Mouse Embryo: Global Activation and Repression of Gene Expression1

  2001cited by this paper
• The Polycomb-Group Gene Ezh2 Is Required for Early Mouse Development

  2001cited by this paper
• Expression of Cre recombinase in mouse oocytes: A means to study maternal effect genes

  2000cited by this paper
• Differential H4 acetylation of paternal and maternal chromatin precedes DNA replication and differential transcriptional activity in pronuclei of 1-cell mouse embryos.

  1997cited by this paper
• Changes in histone synthesis and modification at the beginning of mouse development correlate with the establishment of chromatin mediated repression of transcription.

  1997cited by this paper
• Zp3-cre, a transgenic mouse line for the activation or inactivation of loxP-flanked target genes specifically in the female germ line.

  1997influential reference
• Regulation of Gene Expression at the Beginning of Mammalian Development (*)

  1995cited by this paper
• The transition from maternal to embryonic control in the 2‐cell mouse embryo.

  1982cited by this paper
• Statistical and Structural Approaches to Texture

  year unknowncited by this paper

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  2026cites this paper
• H3K27me3-dependent imprinting and transcriptional regulation in early mouse embryos requires EZHIP-mediated restriction of PRC2 activity

  2026cites this paper
• The Dream and MEC NuRD Complexes reinforce SPR-5/MET-2 maternal reprogramming to maintain the germline-soma distinction

  2025cites this paper
• Mouse and human embryonic genome activation initiate at the one-cell stage

  2025cites this paper
• A comprehensive review of histone modifications during mammalian oogenesis and early embryo development

  2025cites this paper
• LSD1 modulates ovarian reserve establishment by modifying FOXO3 and mitophagy-related genes.

  2025cites this paper
• Effects of oocyte growth on development and histone modification during preimplantation in mouse parthenogenetic embryos.

  2025cites this paper
• Expression of LINE-1 elements is required for preimplantation development and totipotency

  2025cites this paper
• Lysine-specific demethylase 1a is obligatory for gene regulation during kidney development

  2025cites this paper
• Maternal provisioning and zygotic activation: transcriptomic dynamics of early atlantic halibut (Hippoglossus hippoglossus) embryogenesis

  2025cites this paper
• Ectopic transcription due to inherited histone methylation may interfere with the ongoing function of differentiated neurons

  2025cites this paper
• Maternal KLF17 controls zygotic genome activation by acting as a messenger for RNA Pol II recruitment in mouse embryos.

  2024cites this paper
• The impact of retrotransposons on zygotic genome activation and the chromatin landscape of early embryos

  2024cites this paper
• Nuclear receptor-SINE B1 network modulates expanded pluripotency in blastoids and blastocysts

  2024influential citation
• Non-canonical spatial organization of heterochromatin in mouse preimplantation embryos.

  2024cites this paper
• Creation of true interspecies hybrids: Rescue of hybrid class with hybrid cytoplasm affecting growth and metabolism

  2024cites this paper
• Advances in understanding the regulation of pluripotency fate transition in embryonic stem cells

  2024cites this paper
• Exploring the versatility of zygotic genome regulators: A comparative and functional analysis.

  2024cites this paper
• Lysine-specific demethylase 1 (LSD1) participate in porcine early embryonic development by regulating cell autophagy and apoptosis through the mTOR signaling pathway.

  2024cites this paper
• Endogenous retroviruses shape pluripotency specification in mouse embryos

  2024cites this paper
• Antagonistic action of GPS2 and KDM1A at enhancers governs alternative macrophage activation by interleukin 4

  2023cites this paper
• Editorial: The epigenetic control of transposable elements in development and in diseases

  2023cites this paper
• Multi‐Omics Analysis Reveals Translational Landscapes and Regulations in Mouse and Human Oocyte Aging

  2023cites this paper
• Inter and transgenerational impact of H3K4 methylation in neuronal homeostasis

  2023cites this paper
• Gse1, a component of the CoREST complex, is required for placenta development in the mouse.

  2023cites this paper
• H3K4me1 Modification Functions in Caste Differentiation in Honey Bees

  2023cites this paper
• SPR-1/CoREST facilitates the maternal epigenetic reprogramming of the histone demethylase SPR-5/LSD1.

  2023cites this paper
• Maternal Factor Dppa3 Activates 2C-Like Genes and Depresses DNA Methylation in Mouse Embryonic Stem Cells

  2022cites this paper
• Maternal effect genes as risk factors for congenital heart defects

  2022cites this paper
• Histone demethylase Lsd1 is required for the differentiation of neural cells in Nematostella vectensis

  2022cites this paper
• All Quiet on the TE Front? The Role of Chromatin in Transposable Element Silencing

  2022cites this paper
• Transposable Element Dynamics and Regulation during Zygotic Genome Activation in Mammalian Embryos and Embryonic Stem Cell Model Systems

  2021influential citation
• Defining the Role of RBBP4 in Oocyte Maturation and Preimplantation Development Using Trim-Away

  2021cites this paper
• Dynamic changes of histone methylation in mammalian oocytes and early embryos

  2021cites this paper
• Building Pluripotency Identity in the Early Embryo and Derived Stem Cells

  2021cites this paper
• CoREST has a conserved role in facilitating SPR-5/LSD1 maternal reprogramming of histone methylation

  2021cites this paper
• Retinoic acid induces NELFA‐mediated 2C‐like state of mouse embryonic stem cells associates with epigenetic modifications and metabolic processes in chemically defined media

  2021cites this paper
• Aberrant Epigenetic Reprogramming in the First Cell Cycle of Bovine Somatic Cell Nuclear Transfer Embryos

  2021cites this paper
• EHMT2 Controls Transcriptional Noise and the Developmental Switch after Gastrulation in the Mouse Embryo

  2021cites this paper
• Maternal UHRF1 Is Essential for Transcription Landscapes and Repression of Repetitive Elements During the Maternal-to-Zygotic Transition

  2021cites this paper
• Investigating the Inner Cell Mass of the Mouse Blastocyst by Combined Immunofluorescence Staining and RNA Fluorescence In Situ Hybridization.

  2021cites this paper
• Caenorhabditis elegans establishes germline versus soma by balancing inherited histone methylation

  2021cites this paper
• Sex-dependent sensitivity to positive allosteric modulation of GABA action in an APP knock-in mouse model of Alzheimer's disease: Potential epigenetic regulation

  2021cites this paper
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  2021cites this paper
• EHMT2 suppresses the variation of transcriptional switches in the mouse embryo

  2021cites this paper
• Maternal DOT1L is dispensable for mouse development

  2020cites this paper
• Maternal factor NELFA drives a 2C-like state in mouse embryonic stem cells

  2020cites this paper
• Hansel, Gretel, and the Consequences of Failing to Remove Histone Methylation Breadcrumbs

  2020cites this paper
• DUX-miR-344-ZMYM2-Mediated Activation of MERVL LTRs Induces a Totipotent 2C-like State.

  2020cites this paper
• Histone Lysine Demethylases KDM5B and KDM5C Modulate Genome Activation and Stability in Porcine Embryos

  2020cites this paper
• Failure to maternally reprogram histone methylation causes developmental delay due to germline transcription in somatic tissues

  2020cites this paper
• Expression profiling of the Kdm genes in scallop Patinopecten yessoensis suggests involvement of histone demethylation in regulation of early development and gametogenesis.

  2020cites this paper
• Listening to mother: Long‐term maternal effects in mammalian development

  2020cites this paper
• H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos

  2020cites this paper
• Transposon Reactivation in the Germline May Be Useful for Both Transposons and Their Host Genomes

  2020cites this paper
• The H3.3 chaperone Hira complex orchestrates oocyte developmental competence

  2020cites this paper
• C. elegans establishes germline versus soma by balancing inherited histone methylation

  2020cites this paper
• Epigenetic regulation and transcriptional memory in development; selection facilitating prudence.

  2020cites this paper
• Transient Dux expression facilitates nuclear transfer and induced pluripotent stem cell reprogramming

  2020cites this paper
• Strain-Specific Epigenetic Regulation of Endogenous Retroviruses: The Role of Trans-Acting Modifiers

  2020cites this paper
• Histone demethylase Lsd1 is required for the differentiation of neural cells in the cnidarian Nematostella vectensis

  2020cites this paper
• YTHDF2 Regulates Maternal Transcriptome Degradation and Embryo Development in Goat

  2020cites this paper
• Function and Regulation of Histone H3 Lysine-4 Methylation During Oocyte Meiosis and Maternal-to-Zygotic Transition

  2020cites this paper
• The histone lysine demethylase KDM7A is required for normal development and first cell lineage specification in porcine embryos

  2019cites this paper
• Deregulation of the Histone Lysine-Specific Demethylase 1 Is Involved in Human Hepatocellular Carcinoma

  2019cites this paper
• A dual role of dLsd1 in oogenesis: regulating developmental genes and repressing transposons

  2019cites this paper
• Roles and regulation of histone methylation in animal development

  2019cites this paper
• Active Fluctuations of the Nuclear Envelope Shape the Transcriptional Dynamics in Oocytes.

  2019cites this paper
• Perturbation of maternal PIASy abundance disrupts zygotic genome activation and embryonic development via SUMOylation pathway

  2019cites this paper
• Significant improvement of reprogramming efficiency by transient overexpression of ZGA inducer Dux but not Dppa2/4

  2019cites this paper
• Epigenetics of Early Mammalian Development: A Pathway to Regenerative Medicine

  2019cites this paper
• The maternal-to-zygotic transition revisited

  2019cites this paper
• Transcript profiling of bovine embryos implicates specific transcription factors in the maternal-to-embryo transition

  2019cites this paper
• The role and mechanisms of DNA methylation in the oocyte

  2019cites this paper
• EHMT2 and SETDB1 protect the maternal pronucleus from 5mC oxidation

  2019cites this paper
• The maternal to zygotic transition regulates genome-wide heterochromatin establishment in the zebrafish embryo

  2019cites this paper
• Transposable elements drive reorganisation of 3D chromatin during early embryogenesis

  2019cites this paper
• Oocyte Meiotic Maturation

  2019cites this paper
• Regulation of human trophoblast syncytialization by histone demethylase LSD1

  2019cites this paper
• Regulation of human trophoblast syncytialization by histone demethylase LSD1

  2019cites this paper
• Inhibition of lysine-specific histone demethylase 1A results in meiotic aberration during oocyte maturation in vitro in goats.

  2019cites this paper
• Epigenetic Features of Animal Biotechnologies

  2018cites this paper
• Histone 3 lysine 4, 9, and 27 demethylases expression profile in fertilized and cloned bovine and porcine embryos†

  2018cites this paper
• G 9 a regulates temporal preimplantation developmental program 1 and lineage segregation in blastocyst 2 3

  2018cites this paper
• Three-dimensional analysis of nuclear heterochromatin distribution during early development in the rabbit

  2018cites this paper
• Long non-coding RNAs involved in the regulatory network during porcine pre-implantation embryonic development and iPSC induction

  2018cites this paper
• G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

  2018influential citation
• Epigenetic remodeling in preimplantation embryos: cows are not big mice

  2018cites this paper
• The oocyte-to-embryo transition in mouse: past, present, and future†

  2018cites this paper
• Transcriptome Profiling of Single Mouse Oocytes.

  2018cites this paper
• Dynamics of the epigenetic landscape during the maternal-to-zygotic transition

  2018cites this paper
• From Germline to Soma: Epigenetic Dynamics in the Mouse Preimplantation Embryo.

  2018cites this paper
• Active fluctuations modulate gene expression in mouse oocytes

  2018cites this paper
• Mouse oocyte development - Methods and Protocols

  2018influential citation
• CFP1 coordinates histone H3 lysine-4 trimethylation and meiotic cell cycle progression in mouse oocytes

  2018cites this paper
• DCAF13 promotes pluripotency by negatively regulating SUV39H1 stability during early embryonic development

  2018cites this paper
• Nimble and Ready to Mingle: Transposon Outbursts of Early Development.

  2018cites this paper
• Epigenetic regulation in development: is the mouse a good model for the human?

  2018cites this paper
• A Model for Epigenetic Inhibition via Transvection in the Mouse

  2017influential citation