Featured
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| Open AccessGene-expression memory-based prediction of cell lineages from scRNA-seq datasets
Combining experimental lineage tracing with single cell transcriptomics is technically demanding. Here, authors present GEMLI, a computational tool to annotate cell lineages in single cell RNA sequencing data solely based on gene expression.
- A. S. Eisele
- , M. Tarbier
- & D. M. Suter
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Article
| Open AccessThe admixed brushtail possum genome reveals invasion history in New Zealand and novel imprinted genes
The brushtail possum is a treasured Australian marsupial, but also a harmful pest introduced into New Zealand. Here, using functional genomics and a new chromosome-level genome assembly of New Zealand possums, Bond et al. quantify their genome admixture and identify unique parent-specific and weaning associated gene expression.
- Donna M. Bond
- , Oscar Ortega-Recalde
- & Timothy A. Hore
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Article
| Open AccessUnaltered hepatic wound healing response in male rats with ancestral liver injury
How much the environment influences inherited adaptive traits is debated and challenging to demonstrate in mammals. Here the authors performed a multigeneration study that failed to morphologically replicate enhanced wound healing response following ancestral liver injury in rats. However, heritable transcriptional effects suggest transmission at the molecular level, albeit of unclear functional relevance.
- Johanna Beil
- , Juliane Perner
- & Rémi Terranova
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Article
| Open AccessEpigenetic inheritance is unfaithful at intermediately methylated CpG sites
Here the authors question the prevalent view of DNA methylation as a stably inherited epigenetic mark, revealing that the existing model does not apply when considering genomic loci that are intermediately methylated.
- Amir D. Hay
- , Noah J. Kessler
- & Anne C. Ferguson-Smith
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Article
| Open AccessGATA2 mitotic bookmarking is required for definitive haematopoiesis
Most transcription factors detach from chromatin during mitosis, but some are retained and bookmark genomic sites. Here, the authors show that GATA2-mediated mitotic bookmarking is critical for definitive haematopoiesis.
- Rita Silvério-Alves
- , Ilia Kurochkin
- & Carlos-Filipe Pereira
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Article
| Open AccessSNIP1 and PRC2 coordinate cell fates of neural progenitors during brain development
The balance of stem cell maintenance, differentiation, and programmed death is critical for proper development. Here they show that SNIP1 is critical for stem cell survival and differentiation in the developing brain where it acts downstream of TGFb and NFkB and regulates PRC2 activities for governing cell fates.
- Yurika Matsui
- , Mohamed Nadhir Djekidel
- & Jamy C. Peng
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Perspective
| Open AccessEmerging evidence that the mammalian sperm epigenome serves as a template for embryo development
Increasing evidence suggests parental environmental stressors can influence offspring health and disease outcomes. In this perspective, the authors provide an update of the paternal epigenetic inheritance field and propose links between paternally transmitted epigenetic influences and functional changes to the embryo.
- Ariane Lismer
- & Sarah Kimmins
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Article
| Open AccessHistone 4 lysine 5/12 acetylation enables developmental plasticity of Pristionchus mouth form
Developmental plasticity allows organisms to match traits to their environment, however, there are few known molecular mechanisms underlying such plasticity. Here, the authors show that feeding morphs in adult Pristionchus nematodes are set during a critical window in juveniles and identify H4K5/12ac as the environmental information carrier.
- Michael S. Werner
- , Tobias Loschko
- & Ralf J. Sommer
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Article
| Open AccessPaternal methotrexate exposure affects sperm small RNA content and causes craniofacial defects in the offspring
Anti-folate drugs, such as methotrexate, have been largely prohibited for pregnant women because of the teratogenic effect on their descendant. Here, the authors report a intergenerational mechanism by why paternal methotrexate exposure causes craniofacial defects on their offspring.
- Nagif Alata Jimenez
- , Mauricio Castellano
- & Pablo H. Strobl-Mazzulla
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Article
| Open AccessDNMT3B supports meso-endoderm differentiation from mouse embryonic stem cells
DNMT3B-dependent DNA methylation provides epigenetic priming at epiblast stage by methylating enhancers of ectodermal genes to ensure proper differentiation toward mesoendoderm tissues.
- Andrea Lauria
- , Guohua Meng
- & Salvatore Oliviero
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Article
| Open AccessBalanced gene dosage control rather than parental origin underpins genomic imprinting
Here the authors investigate whether for imprinted genes the parent-of-origin of the expressed allele or rather appropriate gene dosage is more important for normal development. Using the differentially methylated region of Dlk1-Dio3 gene involved in imprinting, they show that correct parent-of-origin imprinting pattern is secondary to balanced gene dosage.
- Ariella Weinberg-Shukron
- , Raz Ben-Yair
- & Yonatan Stelzer
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Article
| Open AccessMaternal SMCHD1 regulates Hox gene expression and patterning in the mouse embryo
Parents transmit both genetic and epigenetic information to their offspring, with maternal effect genes being critical regulators of the offspring epigenome. Here they show that maternally deposited SMCHD1 has long-lasting effects on Hox gene expression and vertebral patterning during post-implantation development.
- Natalia Benetti
- , Quentin Gouil
- & Marnie E. Blewitt
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Article
| Open AccessHOX epimutations driven by maternal SMCHD1/LRIF1 haploinsufficiency trigger homeotic transformations in genetically wildtype offspring
Hox genes are known to control anteroposterior patterning, including the vertebrate spine. Here Xue et al. show that maternal Smchd1 regulates Hox expression in an epigenetic manner, and that wild type offspring from heterozygous mothers show skeletal homeotic transformations as a result of this dysregulation.
- Shifeng Xue
- , Thanh Thao Nguyen Ly
- & Bruno Reversade
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Article
| Open AccessThe microRNA cluster C19MC confers differentiation potential into trophoblast lineages upon human pluripotent stem cells
Little is known about the epigenetic mechanisms of the first cell fate commitment in humans. Here, the authors show that activation of the miRNA cluster C19MC confers differentiation potential into trophoblast lineages on human embryonic stem cells.
- Norio Kobayashi
- , Hiroaki Okae
- & Takahiro Arima
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Article
| Open AccessPreventing erosion of X-chromosome inactivation in human embryonic stem cells
Cloutier et al. discover that human embryonic stem cells (hESCs) cultured with media containing inhibitors of GSK3 proteins undergo erosion of X-chromosome inactivation, which equalizes X-linked gene expression between females and males. The findings inform the faithful culture of hESCs.
- Marissa Cloutier
- , Surinder Kumar
- & Sundeep Kalantry
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Article
| Open AccessEpigenetic changes induced by in utero dietary challenge result in phenotypic variability in successive generations of mice
Here the authors show that a high-fat diet in pregnant mice can release silencing of the imprinted Dlk1 locus in multiple generations of offspring. They found that this occurs via changes in microRNA expression at the locus of interest, as well as transcriptional changes across the genome, in the developing oocytes.
- Mathew Van de Pette
- , Andrew Dimond
- & Amanda G. Fisher
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Article
| Open AccessElastic dosage compensation by X-chromosome upregulation
The concerted dynamics of X-chromosome upregulation and X-chromosome inactivation, which collectively balance X-chromosome expression, are not well understood. Using allelic single-cell genomics, the authors characterize the dynamics of X-chromosome upregulation and inactivation along mouse embryonic and stem cell development, calling to question keys aspects of the established model of mammalian dosage compensation.
- Antonio Lentini
- , Huaitao Cheng
- & Björn Reinius
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Article
| Open AccessMalfunction of airway basal stem cells plays a crucial role in pathophysiology of tracheobronchopathia osteoplastica
Tracheobronchopathia osteoplastica (TO), is an underreported affliction characterized by squamous metaplasia and heterotopic bone formation in trachea and bronchi. Here the authors apply functional, as well as genome-wide transcriptional and epigenetic profiling to identify airway basal cells dysfunction underlying TO.
- Yue Hong
- , Shan Shan
- & Tao Ren
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Article
| Open AccessThe control of transcriptional memory by stable mitotic bookmarking
Using quantitative imaging and monitoring transcription in living embryos, Bellec et al., provide evidence that the pioneer factor GAF acts as a stable mitotic bookmarker during early Drosophila development.
- Maëlle Bellec
- , Jérémy Dufourt
- & Mounia Lagha
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Article
| Open AccessLifelong single-cell profiling of cranial neural crest diversification in zebrafish
Cranial neural crest generates a wide diversity of cell types. Here the authors perform single-cell profiling of neural crest to identify key enhancers and transcription factors for cell fate competency, thus revealing progressive acquisition of fate potential.
- Peter Fabian
- , Kuo-Chang Tseng
- & J. Gage Crump
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Article
| Open AccessHistone variant H2A.Z regulates zygotic genome activation
During embryogenesis, the genome becomes transcriptionally active in a process known as zygotic genome activation (ZGA); how ZGA is initiated is still an open question. Here the authors show histone variant H2A.Z deposition precedes RNA polymerase II binding on chromatin, before ZGA. H2A.Z loss causes transcriptional downregulation of ZGA genes and leads to changes in the 3D genome organization.
- Dafne Ibarra-Morales
- , Michael Rauer
- & Nicola Iovino
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Article
| Open AccessEnhancer-associated H3K4 methylation safeguards in vitro germline competence
While inductive signals controlling germline specification are well characterized, the intrinsic factors that allow epiblast cells to respond to such signals remain largely unknown. Here the authors use in vitro differentiated primordial germ cells to show that partial retention of histone H3K4 monomethylation within relevant enhancers is important for germline competence and specification.
- Tore Bleckwehl
- , Giuliano Crispatzu
- & Álvaro Rada-Iglesias
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Article
| Open AccessVertically transferred maternal immune cells promote neonatal immunity against early life infections
Maternal immune cells seed into the foetus during mammalian pregnancy, yet the functional role of these cells is unclear. Here the authors show that maternal immune cells in foetal bone marrow stimulate immune development, subsequently reducing the risk or severity of infections in newborns.
- Ina Annelies Stelzer
- , Christopher Urbschat
- & Petra Clara Arck
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Article
| Open AccessGenomic imprinting in mouse blastocysts is predominantly associated with H3K27me3
In most mammals, imprinted genes contain epigenetic marks that differ in each parental genome and control their parent-of-origin-specific expression. Here, the authors map imprinted genes in mouse preimplantation embryos and find that imprinted gene expression in blastocysts is mainly dependent on Polycomb-mediated H3K27me3-associated gene silencing.
- Laura Santini
- , Florian Halbritter
- & Martin Leeb
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Article
| Open AccessDefective folate metabolism causes germline epigenetic instability and distinguishes Hira as a phenotype inheritance biomarker
Abnormal folate metabolism in mice results in transgenerational epigenetic inheritance of congenital malformations. Here, the authors provide evidence that defective folate metabolism causes germline epigenetic instability and observe multigenerational misexpression of Hira in embryos, implicating Hira transcript levels as a biomarker of maternal phenotypic inheritance.
- Georgina E. T. Blake
- , Xiaohui Zhao
- & Erica D. Watson
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Article
| Open AccessE2F6 initiates stable epigenetic silencing of germline genes during embryonic development
DNA methylation targets CpG island promoters of germline genes to repress their expression in mouse somatic cells. Here the authors show that a transcription factor E2F6 is required to target CpG island DNA methylation and epigenetic silencing to germline genes during early mouse development.
- Thomas Dahlet
- , Matthias Truss
- & Michael Weber
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Article
| Open AccessGermline inherited small RNAs facilitate the clearance of untranslated maternal mRNAs in C. elegans embryos
In animal embryos, maternally deposited mRNAs are degraded by several different mechanisms. Here the authors show that C. elegans embryos inherit antisense pool of small RNAs which are loaded into CSR-1 and cleave complementary maternal mRNAs.
- Piergiuseppe Quarato
- , Meetali Singh
- & Germano Cecere
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Article
| Open AccessGerm granule dysfunction is a hallmark and mirror of Piwi mutant sterility
Piwi deficiency results in sterility and is associated with transposon expression and genomic instability. Here the authors show that sterility of C. elegans Piwi prg-1 mutant is not associated with transposon-induced DNA damage but is associated with and is phenocopied by dysfunction of germ granules.
- Maya Spichal
- , Bree Heestand
- & Shawn Ahmed
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Article
| Open AccessA theoretical model of Polycomb/Trithorax action unites stable epigenetic memory and dynamic regulation
Polycomb (PcG) and Trithorax (TrxG) group regulate several hundred target genes with important roles in development and disease. Here the authors combine experiment and theory to provide evidence that the Polycomb/Trithorax system has the potential for a rich repertoire of regulatory modes beyond simple epigenetic memory.
- Jeannette Reinig
- , Frank Ruge
- & Leonie Ringrose
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Article
| Open AccessChromatin remodeling in bovine embryos indicates species-specific regulation of genome activation
Preimplantation embryos undergo extensive transcriptomic and epigenomic remodeling. Here the authors assay open chromatin in bovine oocytes, embryos, and embryonic stem cells, and compare the transcriptomes and epigenomes of cattle, human and mouse embryos, revealing species-specific regulation of genome activation.
- Michelle M. Halstead
- , Xin Ma
- & Pablo J. Ross
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Article
| Open AccessTransgenerational inheritance of impaired larval T cell development in zebrafish
Evidence for transgenerational inheritance of epigenetic information in vertebrates is scarce. Here the authors report that homozygous dnmt1 mutant zebrafish are essentially normal, with the exception of impaired lymphopoiesis, with impaired larval (but not adult) T cell development being transmitted to subsequent generations by genotypically wildtype fish.
- Norimasa Iwanami
- , Divine-Fondzenyuy Lawir
- & Thomas Boehm
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Article
| Open AccessDEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans
The C. elegans PIWI protein PRG-1 resides in the membraneless organelle P granule. Here, the authors identify the constitutive P granule protein DEPS-1 as an interactor of PRG-1 and show its function in piRNA-dependent silencing. DEPS-1 and PRG-1 form elongated condensates in vivo.
- Kin Man Suen
- , Fabian Braukmann
- & Eric Alexander Miska
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Article
| Open AccessGenome-wide analysis in the mouse embryo reveals the importance of DNA methylation for transcription integrity
DNA methyltrasferases play important role during mouse embryo development. Here the authors reveal the consequences of genetic inactivation of Dnmt1, Dnmt3a and Dnmt3b on the methylome and transcriptome of mouse embryos genome-wide.
- Thomas Dahlet
- , Andrea Argüeso Lleida
- & Michael Weber
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Article
| Open AccessKAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain
Neuronal identity maintenance is highly regulated. Here, the authors showed that CBP and p300 safeguard neuronal identity through histone acetylation at promoters and enhancers of neuronal specific genes. The loss of both CBP and p300 impairs gene expression, circuit activity, and behavior in mice.
- Michal Lipinski
- , Rafael Muñoz-Viana
- & Angel Barco
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Article
| Open AccessReproductive tract extracellular vesicles are sufficient to transmit intergenerational stress and program neurodevelopment
Evidence for sperm small noncoding RNA-mediated intergenerational transmission implies communication from responsive somatic cells to sperm. Here, authors show that epididymal cells alter extracellular vesicle cargo after stress exposure, to impact offspring neurodevelopment and stress reactivity.
- Jennifer C. Chan
- , Christopher P. Morgan
- & Tracy L. Bale
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Article
| Open AccessAssisted reproductive technologies are associated with limited epigenetic variation at birth that largely resolves by adulthood
Use of Assisted Reproductive Technologies (ART) is increasing globally but their impact on long term health remains unclear. Here the authors show that ART-conceived individuals show variation in epigenetic profile at birth that largely resolves by adulthood, with no evidence of an impact on long term outcomes.
- Boris Novakovic
- , Sharon Lewis
- & Richard Saffery
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Article
| Open AccessZebrafish preserve global germline DNA methylation while sex-linked rDNA is amplified and demethylated during feminisation
Germline cells transfer genetic information to offspring, and in zebrafish, drive sex determination. Here the authors report that, unlike mammals, the germline of zebrafish does not undergo genome-wide DNA methylation erasure, while amplifying and demethylating sex-linked rDNA during feminisation.
- Oscar Ortega-Recalde
- , Robert C. Day
- & Timothy A. Hore
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Article
| Open AccessRetention of paternal DNA methylome in the developing zebrafish germline
Germ cells are the means of transferring genetic information to the next generation. Here the authors characterise the DNA methylomes of zebrafish primordial germ cells and find that, unlike mammals, the zebrafish germ cells do not undergo genome-wide DNA demethylation but rather retain paternal DNA methylation patterns
- Ksenia Skvortsova
- , Katsiaryna Tarbashevich
- & Ozren Bogdanovic
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Article
| Open AccessMethylation and PTEN activation in dental pulp mesenchymal stem cells promotes osteogenesis and reduces oncogenesis
Mesenchymal stem cells derived from dental pulp (DP-MSCs) differ in oncogenesic and developmental potential compared to those from bone marrow. Here, the authors show that decreased DNA methylation and histone H3K9Me2 enrichment along with higher PTEN activation in DP-MSCs promotes osteogenesis and reduces oncogenesis.
- Wen-Ching Shen
- , Yung-Chih Lai
- & Shih-Chieh Hung
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Article
| Open AccessSALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation
Human induced pluripotent stem cells (hiPSCs) generate all cell types in the body, but different lines can differ in their potential. Here, the authors determine that higher endogenous levels of SALL3 in hiPSCs lead to ectoderm differentiation bias and reduced mesoderm/endoderm due to DNMT3B mediated DNA methylation.
- Takuya Kuroda
- , Satoshi Yasuda
- & Yoji Sato
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Article
| Open AccessCanonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing
Polycomb Repressive Complexes PRC1 and PRC2 catalyse distinct chromatin modifications to promote gene silencing. Here the authors use reversible tethering of Polycomb proteins to ectopic sites in mouse ESCs and find that canonical but not variant PRC1 can trigger sequence-independent propagation of Polycomb-mediated transcriptional repression.
- Hagar F. Moussa
- , Daniel Bsteh
- & Oliver Bell
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Article
| Open AccessA DNMT3A PWWP mutation leads to methylation of bivalent chromatin and growth retardation in mice
PWWP domains of DNMT3A and DNMT3B are proposed to interact with H3K36me3. Here the authors present a mouse model carrying a D329A point mutation in the DNMT3A PWWP domain and find this causes dominant postnatal growth retardation, with aberrant progressive gain of DNA methylation across domains marked by H3K27me3 in adult tissues.
- Gintarė Sendžikaitė
- , Courtney W. Hanna
- & Gavin Kelsey
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Article
| Open AccessSperm-inherited H3K27me3 impacts offspring transcription and development in C. elegans
The mechanisms of paternal epigenetic inheritance and its influence on offspring are still poorly understood. Here the authors provide evidence that in C. elegans, sperm-inherited chromatin states influence transcription and cell identity in the germ cells of offspring.
- Kiyomi Raye Kaneshiro
- , Andreas Rechtsteiner
- & Susan Strome
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Article
| Open AccessThe non-canonical SMC protein SmcHD1 antagonises TAD formation and compartmentalisation on the inactive X chromosome
The inactive X chromosome (Xi) has an atypical structure, with global loss of TADs, A/B compartments and formation of mega-domains. Here the authors show that the non-canonical SMC family protein, SmcHD1, important for developmental gene silencing on Xi, antagonises TAD formation and compartmentalization on the Xi in a transcription independent way.
- Michal R. Gdula
- , Tatyana B. Nesterova
- & Neil Brockdorff
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Article
| Open AccessBinding of HMGN proteins to cell specific enhancers stabilizes cell identity
HMGN1 and HMGN2 are ubiquitous nucleosome binding proteins. Here the authors provide evidence that HMGN proteins preferentially localize to chromatin regulatory sites to modulate the plasticity of the epigenetic landscape, proposing that HGMNs stabilize, rather than determine, cell identity.
- Bing He
- , Tao Deng
- & Michael Bustin
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Article
| Open AccessAn oviduct-on-a-chip provides an enhanced in vitro environment for zygote genome reprogramming
In vitro culture has detrimental effects on transcriptomes and epigenetic programming of zygotes. Here the authors use microfluidic technology to co-culture bovine oviduct epithelial cells with zygotes and show that the transcriptomes and global methylation patterns of these zygotes are more similar to in vivo zygotes than to conventionally cultured zygotes.
- Marcia A. M. M. Ferraz
- , Hoon Suk Rho
- & Bart M. Gadella
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Article
| Open AccessCaenorhabditis elegans sperm carry a histone-based epigenetic memory of both spermatogenesis and oogenesis
Paternal contributions to epigenetic inheritance via nucleosomes are poorly understood, as sperm in many organisms replace the majority of nucleosomes with protamines. Here the authors provide evidence that Caenorhabditis elegans sperm retain histone packaging of the genome and provide a histone-based epigenetic memory that is important for germ cell development in offspring.
- Tomoko M. Tabuchi
- , Andreas Rechtsteiner
- & Susan Strome
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Article
| Open AccessA stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation
Induced neurons, but not induced pluripotent stem cell (iPSC)-derived neurons, preserve age-related traits. Here, the authors demonstrate that blood-derived induced neural stem cells (iNSCs), despite lacking a pluripotency transit, lose age-related signatures.
- Chao Sheng
- , Johannes Jungverdorben
- & Oliver Brüstle
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Article
| Open AccessLoss of PRC1 induces higher-order opening of Hox loci independently of transcription during Drosophila embryogenesis
Loss of Polycomb repressive complex 1 (PRC1) proteins usually results in both chromatin unfolding and ectopic transcription. Here, the authors analyze the temporal function of two PRC1 proteins during Drosophila embryogenesis and provide evidence that PRC1 maintains gene silencing by folding chromatin domains.
- Thierry Cheutin
- & Giacomo Cavalli