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Chrysanthemums (Chrysanthemum morifolium Ramat.) are ornamental flowers, which are famous worldwide. The mode of inheritance has great implications for the genetic analysis of polyploid species. However, genetic analysis of chrysanthemum has been hampered because of its controversial inheritance mode (disomic or hexasomic). To classify the inheritance mode of chrysanthemums, an analysis of three approaches was carried out inanF1 progeny of 192 offspring using 223 expressed sequence tag-simple sequence repeat (EST-SSR) markers. The analysis included segregation analysis, the ratio of simplex marker alleles linked in coupling to repulsion, as well as the transmission and segregation patterns of EST-SSR marker alleles. After segregation analysis, 204 marker alleles fit hexasomic inheritance and 150 marker alleles fit disomic inheritance, showing that marker alleles were inherited predominantly in a hexasomic manner. Furthermore, the results of the analysis of allele configuration and segregation behavior of five EST-SSR markers also suggested random pairing of chromosomes. Additionally, the ratio of simplex marker alleles linked in coupling to repulsion was 1:0, further supporting hexasomic inheritance. Therefore, it could be inferred that chrysanthemum is a complete or near-complete hexasome. Key words: Chrysanthemum morifolium, EST-SSR, allele dosage, hexasomic, disomic. Les chrysanthemes (Chrysanthemum moriflorum Ramat.) sont des ornementales connues partout dans le monde. Le mode d'heredite a de grandes implications pour l'analyse genetique chez les especes polyplo'ides. Cependant, l'analyse genetique chez les chrysanthemes est compliquee par son heredite controversee (disomi-que ou hexasomique). Pour classifier le mode d'heredite chez les chrysanthemes, une analyse en trois volets a ete realisee chez une progeniture F1 de 192 individus au moyen de 223 marqueurs EST-SSR. Cette etude com-prenait l'analyse de la segregation, le ratio d'alleles simplexes lies en couplage vs en repulsion, ainsi que la transmission et le type de segregation des alleles aux marqueurs EST-SSR. Selon l'analyse de segregation, 204 alleles ont presente une heredite hexasomique et 150 correspondaient a une heredite disomique, mon-trant que l'heredite etait principalement hexasomique. De plus, l'analyse de la configuration des alleles et du comportement en segregation de cinq marqueurs EST-SSR a egalement suggere un appariement aleatoire des chromosomes. De plus, le ratio d'alleles simplexes lies en couplage vs en repulsion (1: 0) appuyait la meme conclusion. Ainsi, il apparait logique d'inferer que le chrysantheme se comporte entierement ou presque entierement en hexasome. [Traduit par la Redaction] Mots-cles: Chrysanthemum moriflorum, EST-SSR, dosaged'alleles, hexasomique, disomique., Introduction Chrysanthemums (Chrysanthemum morifolium Ramat.) are one of the most economically important ornamental crops and are cultivated as cut flowers and potted plants. The cultivated chrysanthemum is hexaploid and aneu-ploid [...]

One of the hallmarks of the cerebral cortex is the extreme diversity of interneurons.sup.1-3. The two largest subtypes of cortical interneurons, parvalbumin- and somatostatin-positive cells, are morphologically and functionally distinct in adulthood but arise from common lineages within the medial ganglionic eminence.sup.4-11. This makes them an attractive model for studying the generation of cell diversity. Here we examine how developmental changes in transcription and chromatin structure enable these cells to acquire distinct identities in the mouse cortex. Generic interneuron features are first detected upon cell cycle exit through the opening of chromatin at distal elements. By constructing cell-type-specific gene regulatory networks, we observed that parvalbumin- and somatostatin-positive cells initiate distinct programs upon settling within the cortex. We used these networks to model the differential transcriptional requirement of a shared regulator, Mef2c, and confirmed the accuracy of our predictions through experimental loss-of-function experiments. We therefore reveal how a common molecular program diverges to enable these neuronal subtypes to acquire highly specialized properties by adulthood. Our methods provide a framework for examining the emergence of cellular diversity, as well as for quantifying and predicting the effect of candidate genes on cell-type-specific development. The transcriptional programs and chromatin accessibility changes that cause two related interneuronal subtypes to diverge from common developmental origins and acquire specialized properties are elucidated., Author(s): Kathryn C. Allaway [sup.1] [sup.2] [sup.3] , Mariano I. Gabitto [sup.4] , Orly Wapinski [sup.3] , Giuseppe Saldi [sup.2] [sup.3] [sup.5] , Chen-Yu Wang [sup.2] [sup.3] , Rachel C. [...]

Paternal and maternal epigenomes undergo marked changes after fertilization.sup.1. Recent epigenomic studies have revealed the unusual chromatin landscapes that are present in oocytes, sperm and early preimplantation embryos, including atypical patterns of histone modifications.sup.2-4 and differences in chromosome organization and accessibility, both in gametes.sup.5-8 and after fertilization.sup.5,8-10. However, these studies have led to very different conclusions: the global absence of local topological-associated domains (TADs) in gametes and their appearance in the embryo.sup.8,9 versus the pre-existence of TADs and loops in the zygote.sup.5,11. The questions of whether parental structures can be inherited in the newly formed embryo and how these structures might relate to allele-specific gene regulation remain open. Here we map genomic interactions for each parental genome (including the X chromosome), using an optimized single-cell high-throughput chromosome conformation capture (HiC) protocol.sup.12,13, during preimplantation in the mouse. We integrate chromosome organization with allelic expression states and chromatin marks, and reveal that higher-order chromatin structure after fertilization coincides with an allele-specific enrichment of methylation of histone H3 at lysine 27. These early parental-specific domains correlate with gene repression and participate in parentally biased gene expression--including in recently described, transiently imprinted loci.sup.14. We also find TADs that arise in a non-parental-specific manner during a second wave of genome assembly. These de novo domains are associated with active chromatin. Finally, we obtain insights into the relationship between TADs and gene expression by investigating structural changes to the paternal X chromosome before and during X chromosome inactivation in preimplantation female embryos.sup.15. We find that TADs are lost as genes become silenced on the paternal X chromosome but linger in regions that escape X chromosome inactivation. These findings demonstrate the complex dynamics of three-dimensional genome organization and gene expression during early development. Single-cell allelic HiC analysis, combined with allelic gene expression and chromatin states, reveals parent-of-origin-specific dynamics of chromosome organization and gene expression during mouse preimplantation development., Author(s): Samuel Collombet [sup.1] [sup.2] , Noémie Ranisavljevic [sup.1] [sup.3] , Takashi Nagano [sup.4] [sup.9] , Csilla Varnai [sup.4] [sup.5] , Tarak Shisode [sup.6] , Wing Leung [sup.4] [sup.9] , [...]

Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes. By contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the three-dimensional organization of the genome results from the interplay of two independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; and cohesin-dependent formation of TADs, possibly by loop extrusion, which helps to guide distant enhancers to their target genes., Author(s): Wibke Schwarzer [1]; Nezar Abdennur [2]; Anton Goloborodko [3]; Aleksandra Pekowska [4]; Geoffrey Fudenberg [5]; Yann Loe-Mie [6, 7]; Nuno A Fonseca [8]; Wolfgang Huber [4]; Christian H. Haering [...]

T-cell receptor (TCR) signalling has a key role in determining T-cell fate. Precursor cells expressing TCRs within a certain low-affinity range for complexes of self-peptide and major histocompatibility complex (MHC) undergo positive selection and differentiate into naive T cells expressing a highly diverse self-MHC-restricted TCR repertoire. In contrast, precursors displaying TCRs with a high affinity for 'self' are either eliminated through TCR-agonist-induced apoptosis (negative selection) (1) or restrained by regulatory T ([T.sub.reg]) cells, whose differentiation and function are controlled by the X-chromosome-encoded transcription factor Foxp3 (reviewed in ref. 2). Foxp3 is expressed in a fraction of self-reactive T cells that escape negative selection in response to agonist-driven TCR signals combined with interleukin 2 (IL-2) receptor signalling. In addition to [T.sub.reg] cells, TCR-agonist-driven selection results in the generation of several other specialized T-cell lineages such as natural killer T cells and innate mucosal-associated invariant T cells (3). Although the latter exhibit a restricted TCR repertoire, [T.sub.reg] cells display a highly diverse collection of TCRs (4-6). Here we explore in mice whether a specialized mechanism enables agonist-driven selection of [T.sub.reg] cells with a diverse TCR repertoire, and the importance this holds for self-tolerance. We show that the intronic Foxp3 enhancer conserved noncoding sequence 3 (CNS3) acts as an epigenetic switch that confers a poised state to the Foxp3 promoter in precursor cells to make [T.sub.reg] cell lineage commitment responsive to a broad range of TCR stimuli, particularly to suboptimal ones. CNS3-dependent expansion of the TCR repertoire enables [T.sub.reg] cells to control self-reactive T cells effectively, especially when thymic negative selection is genetically impaired. Our findings highlight the complementary roles of these two main mechanisms of self-tolerance., TCR signalling plays an essential role in [T.sub.reg] cell differentiation and function (7-10). Previous studies have shown that a broad range of self-reactivity can promote [T.sub.reg] cell differentiation in the [...]

Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable. Keywords: mitochondrial DNA, mitochondrial inheritance, sex determination, paternal leakage, heteroplasmy. L'ADN mitochondrial (l'ADNmt) est principalement herite de la meire chez les eucaryotes. Divers mecanismes moleculaires sous-jacents au phenomeine ont ete decrits, mais les forces evolutives responsables de sa predominance chez les eucaryotes restent encore ai etre elucidees. Des exceptions ai la transmission strictement maternelle de l'ADNmt (<< strict maternal inheritance >> ou SMI) ont ete signalees chez divers taxons eucaryotes, laissant penser que plusieurs nouveaux mecanismes moleculaires de transmission de l'ADNmt existent chez les eucaryotes. Nous proposons que ces mecanismes seront mieux compris en etudiant les exceptions au type predominant de transmission mitochondrial SMI. Cette mini-revue resume les etudes sur les espeices eucaryotes avec des systeimes de transmission mitochondriale inhabituels ou rares, c'est- ai-dire autres que la SMI, tels que la transmission maternelle stable d'une heteroplasmie, la transmission occasionnelle de l'ADNmt paternel (<< paternal leakage >>), la transmission biparentale ou encore strictement paternelle de l'ADNmt et la transmission doublement uniparentale de l'ADNmt. Les geines et les mecanismes impliques dans le controle de la transmission mitochondriale chez ces organismes << deviants >> sont discutes. Le lien etroit entre la transmission mitochondriale et la determination du sexe est egalement aborde, puisque les systeimes atypiques d'heritabilite de l'ADNmt examines dans cette etude sont surtout presents chez des organismes avec des systeimes sexuels rares comme la gynodioecie, la monoecie et l'andromonoecie. L'etude de ces exceptions permettra incontestablement une meilleure comprehension d'un certain nombre de questions fondamentales en biologie, comme l'evolution des mecanismes de transmission de l'ADNmt, la coevolution des genomes nucleaires et mitochondriaux et, peut-etre, le roie des mitochondries dans la determination du sexe. [Traduit par la Redaction] Mots-cles : ADN mitochondrial, transmission mitochondriale, determination du sexe, transmission paternelle occasionnelle, heteroplasmie., Introduction The mitochondrial DNA (mtDNA) codes for some of the genes necessary to produce the proteins required in the oxidative phosphorylation (OXPHOS) reaction that produces ATP. In contrast to the [...]

Upon fertilization, drastic chromatin reorganization occurs during preimplantation development.sup.1. However, the global chromatin landscape and its molecular dynamics in this period remain largely unexplored in humans. Here we investigate chromatin states in human preimplantation development using an improved assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq).sup.2. We find widespread accessible chromatin regions in early human embryos that overlap extensively with putative cis-regulatory sequences and transposable elements. Integrative analyses show both conservation and divergence in regulatory circuitry between human and mouse early development, and between human pluripotency in vivo and human embryonic stem cells. In addition, we find widespread open chromatin regions before zygotic genome activation (ZGA). The accessible chromatin loci are readily found at CpG-rich promoters. Unexpectedly, many others reside in distal regions that overlap with DNA hypomethylated domains in human oocytes and are enriched for transcription factor-binding sites. A large portion of these regions then become inaccessible after ZGA in a transcription-dependent manner. Notably, such extensive chromatin reorganization during ZGA is conserved in mice and correlates with the reprogramming of the non-canonical histone mark H3K4me3, which is uniquely linked to genome silencing.sup.3-5. Taken together, these data not only reveal a conserved principle that underlies the chromatin transition during mammalian ZGA, but also help to advance our understanding of epigenetic reprogramming during human early development and in vitro fertilization.By applying an optimized ATAC-seq protocol to human early embryos, distinct accessible chromatin landscapes are found before and after zygotic genome activation, revealing a marked epigenetic transition during zygotic genome activation and putative regulatory elements wiring human early development., Author(s): Jingyi Wu [sup.1] [sup.7] [sup.8] , Jiawei Xu [sup.2] , Bofeng Liu [sup.1] , Guidong Yao [sup.2] , Peizhe Wang [sup.3] , Zili Lin [sup.1] , Bo Huang [sup.4] [...]

Human epidemiological studies and studies of animal models provide many examples by which early life experiences influence health in a long-term manner, a concept known as biological embedding. Such experiences can have profound impacts during periods of high plasticity in prenatal and early postnatal life. Epigenetic mechanisms influence gene function in the absence of changes in gene sequence. In contrast to the relative stability of gene sequences, epigenetic mechanisms appear, at least to some extent, responsive to environmental signals. To date, a few examples appear to clearly link early social experiences to epigenetic changes in pathways relevant for mental health in adulthood. Our recent work using high-throughput epigenomic techniques points to large-scale changes in gene pathways in addition to candidate genes involved in the response to psychosocial stress and neuroplasticity. Elucidation of which pathways are epigenetically labile under what conditions will enable a more complete understanding of how the epigenome can mediate environmental interactions with the genome that are relevant for mental health. In this mini-review, we provide examples of nascent research into the influence of early life experience on mental health outcomes, discuss evidence of epigenetic mechanisms that may underlie these effects, and describe challenges for research in this area. Key words: epigenetics, DNA methylation, early life adversity, psychiatric disorders, animal models. Des etudes epidemiologiques realisees chez l'humain et des etudes portant sur des modeles animaux fournissent plusieurs exemples dans lesquels des experiences vecues tot dans la vie influencent la sante a long terme, un concept connu sous l'appellation de<>. De telles experiences peuvent avoir de profonds impacts durant les periodes de haute plasticite lors de la vie prenatale et tot apres la naissance. Les mecanismes epigenetiques influencent la fonction des genes en absence de changements dans leur sequence. A la difference de la relative stabilite des sequences geniques, les mecanismes epigenetiques semblent, du moins dans une certaine mesure, repondre aux signaux environnementaux. Jusqu'a present, quelques exemples semblent lier clairement des experiences sociales vecues precocement a des changements epigenetiques dans des sentiers pertinents a la sante mentale a l'age adulte. Nos recents travaux realises a l'aide de techniques epigenomiques a haut debit indiquent la presence de changements a grande echelle dans des sentiers geniques en plus des genes candidats impliques dans la reponse au stress psychosocial et la neuroplasticite. De savoir quels sont les sentiers labiles au plan epigenetique et sous quelles conditions ils le sont nous permettra de mieux comprendre comment l'epigenome peut intervenir dans les interactions de l'environnement avec le genome, qui sont pertinentes a la sante mentale. Dans cette mini-revue, nous donnons des exemples de la recherche emergente portant sur les experiences vecues tot dans la vie et leurs consequences sur la sante mentale, nous discutons des donnees qui revelent que des mecanismes epigenetiques peuvent sous-tendre ces effets, et nous decrivons les defis que pose la recherche dans ce domaine. [Traduit par la Redaction] Mots-cles: epigenetique, methylation d'ADN, epreuves vecues dans l'enfance, maladies psychiatriques, modeles animaux., Biological embedding and mental health The concept of biological embedding has gained substantial traction as a framework for understanding the roots of complex multifactorial phenomena in health and disease (McGowan [...]

DNA methylation is an important epigenetic modification involved in transcriptional regulation, nuclear organization, development, aging, and disease. Although DNA methyltransferases have been characterized, the mechanisms for DNA demethylation remain poorly understood. Using a cell-based reporter assay, we performed a functional genomics screen to identify genes involved in DNA demethylation. Here we show that RNF4 (RING finger protein 4), a SUMO-dependent ubiquitin E3-1igase previously implicated in maintaining genome stability, plays a key role in active DNA demethylation. RNF4 reactivates methylation-silenced reporters and promotes global DNA demethylation. Rnf4 deficiency is embryonic lethal with higher levels of methylation in genomic DNA. Mechanistic studies show that RNF4 interacts with and requires the base excision repair enzymes TDG and APE1 for active demethylation. This activity appears to occur by enhancing the enzymatic activities that repair DNA G:T mismatches generated from methylcytosine deamination. Collectively, our study reveals a unique function for RNF4, which may serve as a direct link between epigenetic DNA demethylation and DNA repair in mammalian cells. epigenetics | DNA repair | base excision repair doi/ 10.1073/pnas.1009025107

Author(s): Hai-Qiang Dai [1, 2]; Bang-An Wang [1, 2]; Lu Yang [3, 4]; Jia-Jia Chen [1, 2]; Guo-Chun Zhu [1, 2]; Mei-Ling Sun [5]; Hao Ge [3]; Rui Wang [3, [...]

Author(s): Marco Sciacovelli [1]; Emanuel Gonalves [2]; Timothy Isaac Johnson [1]; Vincent Roberto Zecchini [1]; Ana Sofia Henriques da Costa [1]; Edoardo Gaude [1]; Alizee Vercauteren Drubbel [1]; Sebastian Julian [...]

MANJEET SINGH PRIZE-1 Effect of SLC47a1 and SLC47a2 Gene Polymorphisms on Glycemic Response to Metformin in Type 2 Diabetes Mellitus Patients of South India Gerard Marshall Raj [sup]1 , Mukta [...]