scholarly journals Zscan4c activates endogenous retrovirus MERVL and cleavage embryo genes

2019 ◽  
Author(s):  
Weiyu Zhang ◽  
Fuquan Chen ◽  
Ruiqing Chen ◽  
Dan Xie ◽  
Jiao Yang ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Embryonic Stem ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Enhancer Activity ◽  
Cell Cleavage ◽  
Cell Embryo ◽  
And Function ◽  
Scan Domain

AbstractEndogenous retroviruses (ERVs) contribute to ∼10 percent of the mouse genome. They are often silenced in differentiated somatic cells but differentially expressed at various embryonic developmental stages. A minority of mouse embryonic stem cells (ESCs), like 2-cell cleavage embryos, highly express ERV MERVL. However, the role of ERVs and mechanism of their activation in these cells are still poorly understood. In this study, we investigated the regulation and function of the stage-specific expressed ERVs, with a particular focus on the totipotency marker MT2/MERVL. We show that the transcription factor Zscan4c functions as an activator of MT2/MERVL and 2-cell/4-cell embryo genes. Zinc finger domains of Zscan4c play an important role in this process. In addition, Zscan4c interacts with MT2 and regulates MT2-nearby 2-cell/4-cell genes through promoting enhancer activity of MT2. Furthermore, MT2 activation is accompanied by enhanced H3K4me1, H3K27ac, and H3K14ac deposition on MT2. Zscan4c also interacts with GBAF chromatin remodelling complex through SCAN domain to further activate MT2 enhancer activity. Taken together, we delineate a previously unrecognized regulatory axis that Zscan4c interacts with and activates MT2/MERVL loci and their nearby genes through epigenetic regulation.

Relief of a repressed gene expression state in the mouse 1-cell embryo requires DNA replication

Development ◽  
1998 ◽  
Vol 125 (16) ◽  
pp. 3153-3166
Author(s):  
S. Forlani ◽  
C. Bonnerot ◽  
S. Capgras ◽  
J.F. Nicolas
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Long Range ◽  
Embryonic Stem ◽  
Hypoxanthine Phosphoribosyl Transferase ◽  
Cell Stage ◽  
Enhancer Activity ◽  
Position Effects ◽  
Cell Proliferation And Differentiation ◽  
Cell Embryo

In the mouse, transcriptional permissiveness is established in the fertilized egg prior to the activation of zygotic genes at the 2-cell stage. Therefore, gene inactivity initiated at the end of gametogenesis results from a complex process, involving more than an inhibition of the basal transcriptional apparatus. We have examined the ability of the first intron (I1) of the human hypoxanthine phosphoribosyl transferase gene, which functions as an enhancer in embryonic stem cells, to activate a reporter gene when placed proximally to or at a distance from the HSV-tk promoter, or when integrated into the mouse genome as part of a stable transgene. In microinjected embryos, I1 functions as an enhancer sequence; however, its competence for long-range activation appears only after the late 1-cell stage and depends on the first DNA replication. Moreover, activation of microinjected transgenes from proximal enhancers occurs in the late 2-cell embryo and in the male pronucleus of 1-cell embryos blocked for DNA replication; whereas, for integrated transgenes, proximal enhancer activity is subject to position effects in the 2-cell embryo and first occurs at the 2- or 4-cell stage, but only after completion of DNA replication. Therefore, the absence of long-range activation and a non-permissive genomic state (the relief of which both depend on DNA replication), together with an inactive transcriptional apparatus, appear to converge to prevent any gene activity in the 1-cell embryo. We propose that the embryo exploits the process of DNA replication to relieve the transcriptionally repressive state that was initially established to fulfil two purposes: (1) to arrest maternal gene expression in the maturing oocyte and (2) to protect the unicellular egg and 1-cell embryo from premature differentiation. Reactivation of gene expression by DNA replication would therefore serve to coordinate cell proliferation and differentiation in the preimplantation embryo.

scholarly journals Hemicentin-1 is an essential extracellular matrix component of the dermal–epidermal and myotendinous junctions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniela Welcker ◽  
Cornelia Stein ◽  
Natalia Martins Feitosa ◽  
Joy Armistead ◽  
Jin-Li Zhang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Developmental Stages ◽  
Cell Types ◽  
Connective Tissues ◽  
Functional Behavior ◽  
Transmission Electron ◽  
Cellular Microenvironments ◽  
And Function ◽  
Myotendinous Junctions

AbstractThe extracellular matrix architecture is composed of supramolecular fibrillar networks that define tissue specific cellular microenvironments. Hemicentins (Hmcn1 and Hmcn2) are ancient and very large members (> 600 kDa) of the fibulin family, whose short members are known to guide proper morphology and functional behavior of specialized cell types predominantly in elastic tissues. However, the tissue distribution and function of Hemicentins within the cellular microenvironment of connective tissues has remained largely unknown. Performing in situ hybridization and immunofluorescence analyses, we found that mouse Hmcn1 and Hmcn2 show a complementary distribution throughout different tissues and developmental stages. In postnatal dermal–epidermal junctions (DEJ) and myotendinous junctions (MTJ), Hmcn1 is primarily produced by mesenchymal cells (fibroblasts, tenocytes), Hmcn2 by cells of epithelial origin (keratinocytes, myocytes). Hmcn1−/− mice are viable and show no overt phenotypes in tissue tensile strength and locomotion tests. However, transmission electron microscopy revealed ultrastructural basement membrane (BM) alterations at the DEJ and MTJ of Hmcn1−/− mice, pointing to a thus far unknown role of Hmcn1 for BM and connective tissue boundary integrity.

scholarly journals A primate-specific retroviral enhancer wires the XACT lncRNA into the core pluripotency network in human

2019 ◽  
Author(s):  
Miguel Casanova ◽  
Madeleine Moscatelli ◽  
Louis Édouard Chauvière ◽  
Christophe Huret ◽  
Julia Samson ◽  
...  
Keyword(s):  
X Chromosome ◽  
Regulatory Networks ◽  
Embryonic Stem ◽  
Endogenous Retroviruses ◽  
Striking Difference ◽  
X Chromosomes ◽  
Regulatory Pathways ◽  
Active Coating ◽  
Species Specific ◽  
And Function

AbstractTransposable elements (TEs) have been of paramount importance in shaping genomic and epigenomic landscapes of their hosts and in driving the expansion of gene regulatory networks during mammalian evolution. They are found in nearly all long non-coding RNAs (lncRNAs) and have promoted their evolution and function, often in a species- and tissue-specific manner. X-chromosome inactivation (XCI) is an essential process that relies on several TE-enriched lncRNAs. While XCI is conserved across species, one striking difference between human and mouse is the existence of XACT (X active coating transcript), a human-specific lncRNA that coats active X chromosomes in pluripotent cells and may oppose X chromosome silencing in this context. Here, we explore how different families of TEs have contributed to shaping the XACT locus and how they couple its expression to pluripotency in humans. Through a combination of sequence analysis across primates, transcriptional interference and genome editing in human embryonic stem cells (hESCs), we identify a critical enhancer for the transcriptional regulation of the XACT locus that evolved from an ancestral group (LTR48B/ERV1) of mammalian endogenous retroviruses (ERVs), prior to the emergence of XACT. Furthermore, we show that this ancient ERV was hijacked by evolutionarily younger hominoid-specific ERVs that gave rise to the promoter of XACT, thus wiring its expression to the pluripotency network. This work illustrates how retroviral-derived sequences may intervene in species-specific regulatory pathways.

scholarly journals The Role of Chromatin Accessibility in cis-Regulatory Evolution

2019 ◽  
Vol 11 (7) ◽  
pp. 1813-1828 ◽  
Author(s):  
Pei-Chen Peng ◽  
Pierre Khoueiry ◽  
Charles Girardot ◽  
James P Reddington ◽  
David A Garfield ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Developmental Stages ◽  
Chromatin Accessibility ◽  
Drosophila Virilis ◽  
Binding Motif ◽  
Evolutionary Divergence ◽  
Core Network ◽  
Enhancer Activity ◽  
Mesoderm Specification

Abstract Transcription factor (TF) binding is determined by sequence as well as chromatin accessibility. Although the role of accessibility in shaping TF-binding landscapes is well recorded, its role in evolutionary divergence of TF binding, which in turn can alter cis-regulatory activities, is not well understood. In this work, we studied the evolution of genome-wide binding landscapes of five major TFs in the core network of mesoderm specification, between Drosophila melanogaster and Drosophila virilis, and examined its relationship to accessibility and sequence-level changes. We generated chromatin accessibility data from three important stages of embryogenesis in both Drosophila melanogaster and Drosophila virilis and recorded conservation and divergence patterns. We then used multivariable models to correlate accessibility and sequence changes to TF-binding divergence. We found that accessibility changes can in some cases, for example, for the master regulator Twist and for earlier developmental stages, more accurately predict binding change than is possible using TF-binding motif changes between orthologous enhancers. Accessibility changes also explain a significant portion of the codivergence of TF pairs. We noted that accessibility and motif changes offer complementary views of the evolution of TF binding and developed a combined model that captures the evolutionary data much more accurately than either view alone. Finally, we trained machine learning models to predict enhancer activity from TF binding and used these functional models to argue that motif and accessibility-based predictors of TF-binding change can substitute for experimentally measured binding change, for the purpose of predicting evolutionary changes in enhancer activity.

scholarly journals On transposons and totipotency

2020 ◽  
Vol 375 (1795) ◽  
pp. 20190339 ◽  
Author(s):  
Maria-Elena Torres-Padilla
Keyword(s):  
Large Scale ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Host Genome ◽  
The Past ◽  
Stage Of Development ◽  
Mammalian Genomes

Our perception of the role of the previously considered ‘selfish’ or ‘junk’ DNA has been dramatically altered in the past 20 years or so. A large proportion of this non-coding part of mammalian genomes is repetitive in nature, classified as either satellites or transposons. While repetitive elements can be termed selfish in terms of their amplification, such events have surely been co-opted by the host, suggesting by itself a likely altruistic function for the organism at the subject of such natural selection. Indeed numerous examples of transposons regulating the functional output of the host genome have been documented. Transposons provide a powerful framework for large-scale relatively rapid concerted regulatory activities with the ability to drive evolution. Mammalian totipotency has emerged as one key stage of development in which transposon-mediated regulation of gene expression has taken centre stage in the past few years. During this period, large-scale (epigenetic) reprogramming must be accomplished in order to activate the host genome. In mice and men, one particular element murine endogenous retrovirus with leucine tRNA primer (MERVL) (and its counterpart human ERVL (HERVL)) appears to have acquired roles as a key driving force in this process. Here, I will discuss and interpret the current knowledge and its implications regarding the role of transposons, particularly of long interspersed nuclear elements (LINE-1s) and endogenous retroviruses (ERVs), in the regulation of totipotency. This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.

scholarly journals Characterization of the Long Terminal Repeat of the Endogenous Retrovirus-derived microRNAs in the Olive Flounder

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hee-Eun Lee ◽  
Ara Jo ◽  
Jennifer Im ◽  
Hee-Jae Cha ◽  
Woo-Jin Kim ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Long Terminal Repeat ◽  
Sequence Similarity ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Terminal Repeat ◽  
Chromosome 9 ◽  
Olive Flounder ◽  
High Sequence Similarity ◽  
Enhancer Activity

Abstract Endogenous retroviruses (ERVs) have been identified at different copy numbers in various organisms. The long terminal repeat (LTR) element of an ERV has the capacity to exert regulatory influence as both a promoter and enhancer of cellular genes. Here, we describe olive flounder (OF)-ERV9, derived from chromosome 9 of the olive flounder. OF-ERV9-LTR provide binding sites for various transcription factors and showed enhancer activity. The OF-ERV9-LTR demonstrates high sequence similarity with the 3′ untranslated region (UTR) of various genes that also contain seed sequences (TGTTTTG) that bind the LTR-derived microRNA(miRNA), OF-miRNA-307. Additionally, OF-miRNA-307 collaborates with transcription factors located in OF-ERV9-LTR to regulate gene expression. Taken together, our data facilitates a greater understanding of the molecular function of OF-ERV families and suggests that OF-miRNA-307 may act as a super-enhancer miRNA regulating gene activity.

The role of human endogenous retroviruses in brain development and function

Apmis ◽  
2016 ◽  
Vol 124 (1-2) ◽  
pp. 105-115 ◽  
Author(s):  
Kristien Mortelmans ◽  
Feng Wang-Johanning ◽  
Gary L. Johanning
Keyword(s):  
Brain Development ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
And Function

scholarly journals DNA methylation directs polycomb-dependent 3D genome re- organisation in naive pluripotency

2019 ◽  
Author(s):  
Katy A McLaughlin ◽  
Ilya M Flyamer ◽  
John P Thomson ◽  
Heidi K Mjoseng ◽  
Ruchi Shukla ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Gene Regulation ◽  
Ground State ◽  
Embryonic Stem ◽  
Genome Organisation ◽  
Dna Hypomethylation ◽  
3D Genome ◽  
And Function

The DNA hypomethylation that occurs when embryonic stem cells (ESCs) are directed to the ground state of naive pluripotency by culturing in 2i conditions results in redistribution of polycomb (H3K27me3) away from its target loci. Here we demonstrate that 3D genome organisation is also altered in 2i. We found chromatin decompaction at polycomb target loci as well as loss of long-range polycomb interactions. By preventing DNA hypomethylation during the transition to the ground-state, we are able to restore the H3K27me3 distribution, and polycomb-mediated 3D genome organisation that is characteristic of primed ESCs grown in serum, to ESCs in 2i. However, these cells retain the functional characteristics of 2i ground state ESCs. Our findings demonstrate the central role of DNA methylation in shaping major aspects of 3D genome organisation but caution against assuming causal roles for the epigenome and 3D genome in gene regulation and function in ESCs.

scholarly journals Identification and Characterization of TUBBY genes in developmental stages of Zea mays

2020 ◽  
Author(s):  
Sendi Mejia ◽  
Suhani Shah ◽  
Yara Abdelsalam ◽  
Ali Nimra ◽  
Munzir Bhatt ◽  
...  
Keyword(s):  
Zea Mays ◽  
Gene Family ◽  
Developmental Stages ◽  
Comparative Approach ◽  
Binding Motifs ◽  
And Function ◽  
Identification And Characterization ◽  
Transcription Factor Gene Family

Abstract In this paper, we studied the organization and function of TUBBY Transcription Factor gene family in maize. Initially, using comparative approach, we discovered the Arabidopsis thaliana orthologs in Zea mays. We found in total 13 genes, 12 of which are orthologs and a unique paralog that exhibits the highest activity in maize. We studied the role of TUBBY gene family across different developmental stages using existing expression data, and discovered the binding motifs present in the promoter region of the genes.

scholarly journals Fine Tuning of Histone Demethylase KDM6A/B Improves the Development of Nuclear Transfer Embryo

2018 ◽  
Author(s):  
Lei Yang ◽  
Lishuang Song ◽  
Xuefei Liu ◽  
Lige Bai ◽  
Guangpeng Li
Keyword(s):  
Nuclear Transfer ◽  
Embryonic Stem ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Fine Tuning ◽  
Mouse Strains ◽  
Low Efficiency ◽  
Nuclear Transfer Embryo ◽  
Genome Activation ◽  
Insight Into

AbstractDespite the success of the production of animals by somatic cell nuclear transfer (SCNT) in many species, the method is limited by a low efficiency. After zygotic genome activation (ZGA), a large number of endogenous retroviruses (ERVs) are expressed, including the murine endogenous retrovirus-L (MuERVL/MERVL). In this study, we generated a series of MERVL-reporter mouse strains to detect the ZGA event in embryos. We found that the majority of SCNT embryos exhibited ZGA failure, and histone H3 lysine 27 trimethylation (H3K27me3) prevented SCNT reprogramming. Overexpression of the H3K27me3-specific demethylase KDM6A, but not KDM6B, improved the efficiency of SCNT. Conversely, knockdown KDM6B not only facilitate ZGA, but also impede ectopic Xist expression in SCNT reprogramming. Furthermore, the knockdown of KDM6B increased the rate of SCNT-derived Duchenne muscular dystrophy embryonic stem cell establishment, indicate that these results not only provide insight into the mechanisms underlying failures of SCNT, but also may extend the applications of SCNT.

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