THE ROLE OF TRANSPOSABLE ELEMENTS IN ENDOCRINE CHANGES DURING AGING

Author(s):  
Р. Н. Мустафин ◽  
Э. К. Хуснутдинова

Одним из ключевых механизмов старения является изменение гормональной регуляции, для эффективного воздействия на которую с целью продления жизни необходимо определение первопричины данных процессов. В качестве молекулярных драйверов, управляющих динамикой уровня гормонов, могут служить транспозоны. Это связано с их использованием в качестве источников нуклеотидных последовательностей, воспринимающих специфические сигналы рибозимов, транскрипционных факторов, гормонов и их мессенджеров. В то же время, в эволюции транспозоны являются источниками рибозимов и белков, обладающих ДНК-связывающими доменами. Начиная с деления зиготы, видоспецифический состав и распределение транспозонов в геноме могут использоваться как биологическая кодировка, необходимая для последовательной и специфической для типов клеток экспрессии генов. Сделано предположение, что гормональная регуляция является одним из компонентов сложной системы управления онтогенезом под влиянием мобильных элементов. В качестве подтверждения приведены работы о роли транспозонов в управлении генами эндокринной системы, а также о влиянии гормонов на активность транспозонов. Исследование этих взаимосвязей может иметь перспективы для разработки методов продления жизни, так как эпигенетические изменения под влиянием транспозонов носят обратимый характер. Species-specific changes in the endocrine system are key factors in aging. Therefore, to prolong life, it is necessary to find regulators of the highest level, the changes of which lead to physiological aging. The molecular drivers that control dynamics of hormone levels can be transposons. This is due to the use of nucleotide sequences of transposons as binding sites that perceive specific signals of ribozymes, transcription factors, hormones and their messengers. At the same time, transposons are evolutionary sources of ribozymes and proteins that have DNA-binding domains. Starting from zygote division, the species-specific composition and distribution of transposons in the genome serves as a biological coding, which is necessary for the sequential expression of genes specific to cell types and stage of development. We suggest that hormonal regulation is one of the components of this complex system of regulation of ontogenesis under the control of transposons. To confirm our hypothesis, this review contains articles that prove the importance of transposons for species-specific control of endocrine system genes, as well as the effect of hormones on transposon activity. The research of these relationships is promising for the development of methods for the effective prolongation of life, since epigenetic changes under the influence of transposons are reversible.

2019 ◽  
Vol 9 (12) ◽  
pp. 359 ◽  
Author(s):  
Gergely Jocsak ◽  
Eniko Ioja ◽  
David Sandor Kiss ◽  
Istvan Toth ◽  
Zoltan Barany ◽  
...  

The endocrine system of animals consists of fine-tuned self-regulating mechanisms that maintain the hormonal and neuronal milieu during tissue development. This complex system can be influenced by endocrine disruptors (ED)—substances that can alter the hormonal regulation even in small concentrations. By now, thousands of substances—either synthesized by the plastic, cosmetic, agricultural, or medical industry or occurring naturally in plants or in polluted groundwater—can act as EDs. Their identification and testing has been a hard-to-solve problem; Recent indications that the ED effects may be species-specific just further complicated the determination of biological ED effects. Here we compare the effects of bisphenol-A, zearalenone, and arsenic (well-known EDs) exerted on mouse and rat neural cell cultures by measuring the differences of the ED-affected neural estrogen- and thyroid receptors. EDs alters the receptor expression in a species-like manner detectable in the magnitude as well as in the nature of biological responses. It is concluded that the interspecies differences (or species specificity) in ED effects should be considered in the future testing of ED effects.


eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Jessica K Cinkornpumin ◽  
Dona R Wisidagama ◽  
Veronika Rapoport ◽  
James L Go ◽  
Christoph Dieterich ◽  
...  

Nematodes and insects are the two most speciose animal phyla and nematode–insect associations encompass widespread biological interactions. To dissect the chemical signals and the genes mediating this association, we investigated the effect of an oriental beetle sex pheromone on the development and behavior of the nematode Pristionchus pacificus. We found that while the beetle pheromone is attractive to P. pacificus adults, the pheromone arrests embryo development, paralyzes J2 larva, and inhibits exit of dauer larvae. To uncover the mechanism that regulates insect pheromone sensitivity, a newly identified mutant, Ppa-obi-1, is used to reveal the molecular links between altered attraction towards the beetle pheromone, as well as hypersensitivity to its paralyzing effects. Ppa-obi-1 encodes lipid-binding domains and reaches its highest expression in various cell types, including the amphid neuron sheath and excretory cells. Our data suggest that the beetle host pheromone may be a species-specific volatile synomone that co-evolved with necromeny.


1996 ◽  
Vol 16 (4) ◽  
pp. 1316-1325 ◽  
Author(s):  
S Mink ◽  
U Kerber ◽  
K H Klempnauer

The retroviral oncogene v-myb encodes a transcription factor (v-Myb) which activates the myelomonocyte-specific mim-1 gene, a natural myb target gene, by cooperating with members of the C/EBP transcription factor family. The finding that v-Myb, together with C/EBP, is sufficient to activate the mim-1 gene in heterologous cell types has implicated Myb and C/EBP as a bipartite molecular switch, which regulates the expression of myelomonocyte-specific genes. To understand the relationship between v-Myb and C/EBP in more detail, we have examined the molecular basis of the activation of the mim-1 promoter by v-Myb and C/EBPbeta, a member of the C/EBP transcription factor family highly expressed in myelomonocytic cells. We have identified a composite Myb and C/EBP response element which mediates synergistic activation of the mim-1 promoter by both factors and consists of closely spaced Myb- and C/EBP-binding sites. In vitro and in vivo protein-binding studies indicate that v-Myb and C/EBPbeta interact with each other via their DNA-binding domains. We show that this interaction is essential for the synergistic activation of the mim-1 promoter by v-Myb and C/EBPbeta. Our work therefore identifies C/EBPbeta as an interaction partner of v-Myb involved in myelomonocyte gene expression.


2021 ◽  
Vol 22 (13) ◽  
pp. 7043
Author(s):  
Shaida Ouladan ◽  
Alex Gregorieff

Despite the environmental constraints imposed upon the intestinal epithelium, this tissue must perform essential functions such as nutrient absorption and hormonal regulation, while also acting as a critical barrier to the outside world. These functions depend on a variety of specialized cell types that are constantly renewed by a rapidly proliferating population of intestinal stem cells (ISCs) residing at the base of the crypts of Lieberkühn. The niche components and signals regulating crypt morphogenesis and maintenance of homeostatic ISCs have been intensely studied over the last decades. Increasingly, however, researchers are turning their attention to unraveling the mechanisms driving gut epithelial regeneration due to physical damage or infection. It is now well established that injury to the gut barrier triggers major cell fate changes, demonstrating the highly plastic nature of the gut epithelium. In particular, lineage tracing and transcriptional profiling experiments have uncovered several injury-induced stem-cell populations and molecular markers of the regenerative state. Despite the progress achieved in recent years, several questions remain unresolved, particularly regarding the mechanisms driving dedifferentiation of the gut epithelium. In this review, we summarize the latest studies, primarily from murine models, that define the regenerative processes governing the gut epithelium and discuss areas that will require more in-depth investigation.


2014 ◽  
Vol 289 (31) ◽  
pp. 21605-21616 ◽  
Author(s):  
Shuo Wang ◽  
Miles H. Linde ◽  
Manoj Munde ◽  
Victor D. Carvalho ◽  
W. David Wilson ◽  
...  

2003 ◽  
Vol 278 (25) ◽  
pp. 22586-22595 ◽  
Author(s):  
Alpana Ray ◽  
Papiya Ray ◽  
Nicole Guthrie ◽  
Arvind Shakya ◽  
Deepak Kumar ◽  
...  

2004 ◽  
Vol 3 (5) ◽  
pp. 1111-1123 ◽  
Author(s):  
Susan Nicholls ◽  
Melissa Straffon ◽  
Brice Enjalbert ◽  
André Nantel ◽  
Susan Macaskill ◽  
...  

ABSTRACT In Saccharomyces cerevisiae, the (C2H2)2 zinc finger transcription factors Msn2 and Msn4 play central roles in responses to a range of stresses by activating gene transcription via the stress response element (STRE; CCCCT). The pathogen Candida albicans displays stress responses that are thought to help it survive adverse environmental conditions encountered within its human host. However, these responses differ from those in S. cerevisiae, and hence we predicted that the roles of Msn2- and Msn4-like proteins might have been functionally reassigned in C. albicans. C. albicans has two such proteins: CaMsn4 and Mnl1 (for Msn2- and Msn4-like). CaMSN4, but not MNL1, weakly complemented the inability of an S. cerevisiae msn2 msn4 mutant to activate a STRE-lacZ reporter. Also, the disruption of CaMsn4 and Mnl1 had no discernible effect upon the resistance of C. albicans to heat, osmotic, ethanol, nutrient, oxidative, or heavy-metal stress or upon the stress-activated transcriptome in C. albicans. Furthermore, although Cap1-dependent activation of a Yap response element-luciferase reporter was observed, a STRE reporter was not activated in response to stresses in C. albicans. Ectopic expression of CaMsn4 or Mnl1 did not affect the cellular or molecular responses of C. albicans to stress. Under the conditions tested, the putative activation and DNA binding domains of CaMsn4 did not appear to be functional. These data suggest that CaMsn4 and Mnl1 do not contribute significantly to stress responses in C. albicans. The data are consistent with the idea that stress signaling in this fungus has diverged significantly from that in budding yeast.


2005 ◽  
Vol 79 (13) ◽  
pp. 8661-8664 ◽  
Author(s):  
Stephen Schuck ◽  
Arne Stenlund

ABSTRACT Viral initiator proteins are polypeptides that form oligomeric complexes on the origin of DNA replication (ori). These complexes carry out a multitude of functions related to initiation of DNA replication, and although many of these functions have been characterized biochemically, little is understood about how the complexes are assembled. Here we demonstrate that loss of one particular interaction, the dimerization between E1 DNA binding domains, has a severe effect on DNA replication in vivo but has surprisingly modest effects on most individual biochemical activities in vitro. We conclude that the dimer interaction is primarily required for initial recognition of ori.


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