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 Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zi Wang ◽  
Pan Wang ◽  
Yanan Li ◽  
Hongling Peng ◽  
Yu Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Hematological Malignancies ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Hematologic Disorders ◽  
Cell Lineages ◽  
Stage Of Development ◽  
Transcription Complexes ◽  
Insight Into

AbstractHematopoiesis requires finely tuned regulation of gene expression at each stage of development. The regulation of gene transcription involves not only individual transcription factors (TFs) but also transcription complexes (TCs) composed of transcription factor(s) and multisubunit cofactors. In their normal compositions, TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis. The integration of posttranslational and conformational modifications in the chromatin landscape, nucleosomes, histones and interacting components via the cofactor–TF interplay is critical to optimal TF activity. Mutations or translocations of cofactor genes are expected to alter cofactor–TF interactions, which may be causative for the pathogenesis of various hematologic disorders. Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy. In this review, we summarize the current knowledge regarding the models and functions of cofactor–TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies. This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.

scholarly journals Mobilization of Endogenous Retroviruses in Mice after Infection with an Exogenous Retrovirus

2008 ◽  
Vol 83 (6) ◽  
pp. 2429-2435 ◽  
Author(s):  
Leonard H. Evans ◽  
A. S. M. Alamgir ◽  
Nick Owens ◽  
Nick Weber ◽  
Kimmo Virtaneva ◽  
...  
Keyword(s):  
Germ Line ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Gene Sequences ◽  
Endogenous Viruses ◽  
Mammalian Genomes ◽  
Leukemia Viruses ◽  
Retroviral Infections ◽  
Ecotropic Virus ◽  
Rna Transcript

ABSTRACT Mammalian genomes harbor a large number of retroviral elements acquired as germ line insertions during evolution. Although many of the endogenous retroviruses are defective, several contain one or more intact viral genes that are expressed under certain physiological or pathological conditions. This is true of the endogenous polytropic retroviruses that generate recombinant polytropic murine leukemia viruses (MuLVs). In these recombinants the env gene sequences of exogenous ecotropic MuLVs are replaced with env gene sequences from an endogenous polytropic retrovirus. Although replication-competent endogenous polytropic retroviruses have not been observed, the recombinant polytropic viruses are capable of replicating in numerous species. Recombination occurs during reverse transcription of a virion RNA heterodimer comprised of an RNA transcript from an endogenous polytropic virus and an RNA transcript from an exogenous ecotropic MuLV RNA. It is possible that homodimers corresponding to two full-length endogenous RNA genomes are also packaged. Thus, infection by an exogenous virus may result not only in recombination with endogenous sequences, but also in the mobilization of complete endogenous retrovirus genomes via pseudotyping within exogenous retroviral virions. We report that the infection of mice with an ecotropic virus results in pseudotyping of intact endogenous viruses that have not undergone recombination. The endogenous retroviruses infect and are integrated into target cell genomes and subsequently replicate and spread as pseudotyped viruses. The mobilization of endogenous retroviruses upon infection with an exogenous retrovirus may represent a major interaction of exogenous retroviruses with endogenous retroviruses and may have profound effects on the pathogenicity of retroviral infections.

scholarly journals MysTR: an Endogenous Retrovirus Family in Mammals That Is Undergoing Recent Amplifications to Unprecedented Copy Numbers

2005 ◽  
Vol 79 (23) ◽  
pp. 14698-14707 ◽  
Author(s):  
Michael A. Cantrell ◽  
Martina M. Ederer ◽  
Issac K. Erickson ◽  
Vicki J. Swier ◽  
Robert J. Baker ◽  
...  
Keyword(s):  
Repetitive Sequences ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
South American ◽  
Coding Regions ◽  
Copy Numbers ◽  
Species Analysis ◽  
Outgroup Species ◽  
Mammalian Genomes ◽  
Oryzomys Palustris

ABSTRACT A large percentage of the repetitive elements in mammalian genomes are retroelements, which have been moved primarily by LINE-1 retrotransposons and endogenous retroviruses. Although LINE-1 elements have remained active throughout the mammalian radiation, specific groups of endogenous retroviruses generally remain active for comparatively shorter periods of time. Identification of an unusual extinction of LINE-1 activity in a group of South American rodents has opened a window for examination of the interplay in mammalian genomes between these ubiquitous retroelements. In the course of a search for any type of repetitive sequences whose copy numbers have substantially changed in Oryzomys palustris, a species that has lost LINE-1 activity, versus Sigmodon hispidus, a closely related species retaining LINE-1 activity, we have identified an endogenous retrovirus family differentially amplified in these two species. Analysis of three full-length, recently transposed copies, called mysTR elements, revealed gag, pro, and pol coding regions containing stop codons which may have accumulated either before or after retrotransposition. Isolation of related sequences in S. hispidus and the LINE-1 active outgroup species, Peromyscus maniculatus, by PCR of a pro-pol region has allowed determination of copy numbers in each species. Unusually high copy numbers of approximately 10,000 in O. palustris versus 1,000 in S. hispidus and 4,500 in the more distantly related P.maniculatus leave open the question of whether there is a connection between endogenous retrovirus activity and LINE-1 inactivity. Nevertheless, these independent expansions of mysTR represent recent amplifications of this endogenous retrovirus family to unprecedented levels.

Since 1945: New Amenities, New Hazards

2000 ◽  
Author(s):  
William B. Meyer
Keyword(s):  
New York ◽  
Large Scale ◽  
Social Scientist ◽  
World History ◽  
The United States ◽  
Economic Role ◽  
The Past ◽  
American Society ◽  
Service Employment

If the average citizen's surroundings defined the national climate, then the United States grew markedly warmer and drier in the postwar decades. Migration continued to carry the center of population west and began pulling it southward as well. The growth of what came to be called the Sunbelt at the "Snowbelt's" expense passed a landmark in the early 1960s when California replaced New York as the most populous state. Another landmark was established in the early 1990s when Texas moved ahead of New York. In popular discussion, it was taken for granted that finding a change of climate was one of the motives for relocating as well as one of the results. It was not until 1954, though, that an American social scientist first seriously considered the possibility. The twentieth-century flow of Americans to the West Coast, the geographer Edward L. Ullman observed in that year, had no precedent in world history. It could not be explained by the theories of settlement that had worked well in the past, for a substantial share of it represented something entirely new, "the first large-scale in-migration to be drawn by the lure of a pleasant climate." If it was the first of its kind, it was unlikely to be the last. For a set of changes in American society, Ullman suggested, had transformed the economic role of climate. The key changes included a growth in the numbers of pensioned retirees; an increase in trade and service employment, much more "footloose" than agriculture or manufacturing was; developments in technology making manufacturing itself more footloose; and a great increase in mobility brought about by the automobile and the highway. All in one way or another had weakened the bonds of place and made Americans far freer than before to choose where to live. Whatever qualities made life in any spot particularly pleasant thus attracted migration more than in the past. Ullman grouped such qualities together as "amenities." They ranged from mountains to beaches to cultural attractions, but climate appeared to be the most important, not least because it was key to the enjoyment of many of the rest. Ullman did not suppose that all Americans desired the same climate. For most people, in this as in other respects, "where one was born and lives is the best place in the world, no matter how forsaken a hole it may appear to an outsider."

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.

Getting to Scale with Good Educational Practice

1996 ◽  
Vol 66 (1) ◽  
pp. 1-27 ◽  
Author(s):  
Richard Elmore
Keyword(s):  
Curriculum Reform ◽  
Large Scale ◽  
Educational Practice ◽  
School Organization ◽  
Progressive Movement ◽  
Successful Teachers ◽  
The Past ◽  
Incentive Structures ◽  
Children And Young Adults

How can good educational practice move beyond pockets of excellence to reach a much greater proportion of students and educators? While many children and young adults in school districts and communities around the country have long benefited from the tremendous accomplishments of successful teachers, schools, and programs, replicating this success on a larger scale has proven to be a difficult and vexing issue. In this article, Richard Elmore addresses this problem by analyzing the role of school organization and incentive structures in thwarting large-scale adoption of innovative practices close to the "core" of educational practice. Elmore then reviews evidence from two attempts at large-scale reform in the past — the progressive movement and the National Science Foundation curriculum reform projects — to evaluate his claims that ambitious large-scale school reform efforts, under current conditions, will be ineffective and transient. He concludes with four detailed recommendations for addressing the issue of scale in improving practice in education.

scholarly journals Quantitative Modeling of Protein Synthesis Using Ribosome Profiling Data

2021 ◽  
Vol 8 ◽  
Author(s):  
Vandana Yadav ◽  
Inayat Ullah Irshad ◽  
Hemant Kumar ◽  
Ajeet K. Sharma
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Translation Initiation ◽  
Regulation Of Gene Expression ◽  
Ribosome Profiling ◽  
Quantitative Modeling ◽  
Quantitative Prediction ◽  
Translation Rate ◽  
The Past

Quantitative prediction on protein synthesis requires accurate translation initiation and codon translation rates. Ribosome profiling data, which provide steady-state distribution of relative ribosome occupancies along a transcript, can be used to extract these rate parameters. Various methods have been developed in the past few years to measure translation-initiation and codon translation rates from ribosome profiling data. In the review, we provide a detailed analysis of the key methods employed to extract the translation rate parameters from ribosome profiling data. We further discuss how these approaches were used to decipher the role of various structural and sequence-based features of mRNA molecules in the regulation of gene expression. The utilization of these accurate rate parameters in computational modeling of protein synthesis may provide new insights into the kinetic control of the process of gene expression.

scholarly journals Thyroid Hormone Plays an Important Role in Cardiac Function: From Bench to Bedside

2021 ◽  
Vol 12 ◽  
Author(s):  
Hiroyuki Yamakawa ◽  
Tomoko S. Kato ◽  
Jaeduk Yoshimura Noh ◽  
Shinsuke Yuasa ◽  
Akio Kawamura ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Cardiac Function ◽  
Cardiovascular System ◽  
Antiarrhythmic Agent ◽  
Current Knowledge ◽  
Cardiac Contractility ◽  
The Body ◽  
The Past ◽  
Systolic And Diastolic Function

Thyroid hormones (THs) are synthesized in the thyroid gland, and they circulate in the blood to regulate cells, tissues, and organs in the body. In particular, they exert several effects on the cardiovascular system. It is well known that THs raise the heart rate and cardiac contractility, improve the systolic and diastolic function of the heart, and decrease systemic vascular resistance. In the past 30 years, some researchers have studied the molecular pathways that mediate the role of TH in the cardiovascular system, to better understand its mechanisms of action. Two types of mechanisms, which are genomic and non-genomic pathways, underlie the effects of THs on cardiomyocytes. In this review, we summarize the current knowledge of the action of THs in the cardiac function, the clinical manifestation and parameters of their hemodynamics, and treatment principles for patients with hyperthyroid- or hypothyroid-associated heart disease. We also describe the cardiovascular drugs that induce thyroid dysfunction and explain the mechanism underlying the thyroid toxicity of amiodarone, which is considered the most effective antiarrhythmic agent. Finally, we discuss the recent reports on the involvement of thyroid hormones in the regulation of myocardial regeneration and metabolism in the adult heart.

scholarly journals Tight junction proteins in gastrointestinal and liver disease

Gut ◽  
2018 ◽  
Vol 68 (3) ◽  
pp. 547-561 ◽  
Author(s):  
Mirjam B Zeisel ◽  
Punita Dhawan ◽  
Thomas F Baumert
Keyword(s):  
Liver Disease ◽  
Tight Junction ◽  
Functional Role ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Causative Role ◽  
Mesenchymal Transition ◽  
Disease Biology

Over the past two decades a growing body of evidence has demonstrated an important role of tight junction (TJ) proteins in the physiology and disease biology of GI and liver disease. On one side, TJ proteins exert their functional role as integral proteins of TJs in forming barriers in the gut and the liver. Furthermore, TJ proteins can also be expressed outside TJs where they play important functional roles in signalling, trafficking and regulation of gene expression. A hallmark of TJ proteins in disease biology is their functional role in epithelial-to-mesenchymal transition. A causative role of TJ proteins has been established in the pathogenesis of colorectal cancer and gastric cancer. Among the best characterised roles of TJ proteins in liver disease biology is their function as cell entry receptors for HCV—one of the most common causes of hepatocellular carcinoma. At the same time TJ proteins are emerging as targets for novel therapeutic approaches for GI and liver disease. Here we review our current knowledge of the role of TJ proteins in the pathogenesis of GI and liver disease biology and discuss their potential as therapeutic targets.

scholarly journals MiRNAs in the Peri-Implantation Period: Contribution to Embryo–Maternal Communication in Pigs

2020 ◽  
Vol 21 (6) ◽  
pp. 2229 ◽  
Author(s):  
Monika M. Kaczmarek ◽  
Joanna Najmula ◽  
Maria M. Guzewska ◽  
Emilia Przygrodzka
Keyword(s):  
Current Knowledge ◽  
Mammalian Species ◽  
Embryo Implantation ◽  
Cell Communication ◽  
Large Family ◽  
Protein Coding ◽  
The Past ◽  
Domestic Livestock ◽  
Implantation Period

MicroRNAs (miRNAs) constitute a large family of noncoding RNAs, approximately 22 nucleotides long, which function as guide molecules in RNA silencing. Targeting most protein-coding transcripts, miRNAs are involved in nearly all developmental and pathophysiological processes in animals. To date, the regulatory roles of miRNAs in reproduction, such as fertilization, embryo development, implantation, and placenta formation, among others, have been demonstrated in numerous mammalian species, including domestic livestock such as pigs. Over the past years, it appeared that understanding the functions of miRNAs in mammalian reproduction can substantially improve our understanding of the biological challenges of successful reproductive performance. This review describes the current knowledge on miRNAs, specifically in relation to the peri-implantation period when the majority of embryonic mortality occurs in pigs. To present a broader picture of crucial peri-implantation events, we focus on the role of miRNA-processing machinery and miRNA–mRNA infarctions during the maternal recognition of pregnancy, leading to maintenance of the corpus luteum function and further embryo implantation. Furthermore, we summarize the current knowledge on cell-to-cell communication involving extracellular vesicles at the embryo–maternal interface in pigs. Finally, we discuss the potential of circulating miRNAs to serve as indicators of ongoing embryo–maternal crosstalk.

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