scholarly journals Epigenetic Modifications During Sex Change Repress Gonadotropin Stimulation of Cyp19a1a in a Teleost Ricefield Eel (Monopterus albus)

Endocrinology ◽  
2013 ◽  
Vol 154 (8) ◽  
pp. 2881-2890 ◽  
Author(s):  
Yang Zhang ◽  
Shen Zhang ◽  
Zhixin Liu ◽  
Lihong Zhang ◽  
Weimin Zhang
Keyword(s):  
Dna Methylation ◽  
Binding Protein ◽  
Sex Change ◽  
Gonadal Development ◽  
Proximal Region ◽  
Histone Deacetylation ◽  
Epigenetic Mechanisms ◽  
Gonadal Differentiation ◽  
Stimulation Of

Abstract In vertebrates, cytochrome P450 aromatase, encoded by cyp19a1, converts androgens to estrogens and plays important roles in gonadal differentiation and development. The present study examines whether epigenetic mechanisms are involved in cyp19a1a expression and subsequent gonadal development in the hermaphroditic ricefield eel. The expression of the ricefield eel cyp19a1a was stimulated by gonadotropin via the cAMP pathway in the ovary but not the ovotestis or testis. The CpG within the cAMP response element (CRE) of the cyp19a1a promoter was hypermethylated in the ovotestis and testis compared with the ovary. The methylation levels of CpG sites around CRE in the distal region (region II) and around steroidogenic factor 1/adrenal 4 binding protein sites and TATA box in the proximal region (region I) were inversely correlated with cyp19a1a expression during the natural sex change from female to male. In vitro DNA methylation decreased the basal and forskolin-induced activities of cyp19a1a promoter. Chromatin immunoprecipitation assays indicated that histone 3 (Lys9) in both regions I and II of the cyp19a1a promoter were deacetylated and trimethylated in the testis, and in contrast to the ovary, phosphorylated CRE-binding protein failed to bind to these regions. Lastly, the DNA methylation inhibitor 5-aza-2′-deoxycytidine reversed the natural sex change of ricefield eels. These results suggested that epigenetic mechanisms involving DNA methylation and histone deacetylation and methylation may abrogate the stimulation of cyp19a1a by gonadotropins in a male-specific fashion. This may be a mechanism widely used to drive natural sex change in teleosts as well as gonadal differentiation in other vertebrates.

scholarly journals Regulation of Poly(ADP-Ribose) Polymerase 1 Activity by Y-Box-Binding Protein 1

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1325
Author(s):  
Konstantin N. Naumenko ◽  
Mariya V. Sukhanova ◽  
Loic Hamon ◽  
Tatyana A. Kurgina ◽  
Elizaveta E. Alemasova ◽  
...  
Keyword(s):  
Ternary Complex ◽  
Binding Protein ◽  
Terminal Part ◽  
Force Microscopy ◽  
Atomic Force ◽  
Synthesis Activity ◽  
Positively Charged ◽  
Stimulation Of ◽  
Damaged Dna

Y-box-binding protein 1 (YB-1) is a multifunctional positively charged protein that interacts with DNA or RNA and poly(ADP-ribose) (PAR). YB-1 is poly(ADP-ribosyl)ated and stimulates poly(ADP-ribose) polymerase 1 (PARP1) activity. Here, we studied the mechanism of YB-1-dependent PAR synthesis by PARP1 in vitro using biochemical and atomic force microscopy assays. PAR synthesis activity of PARP1 is known to be facilitated by co-factors such as Mg2+. However, in contrast to an Mg2+-dependent reaction, the activation of PARP1 by YB-1 is accompanied by overall up-regulation of protein PARylation and shortening of the PAR polymer. Therefore, YB-1 and cation co-factors stimulated PAR synthesis in divergent ways. PARP1 autoPARylation in the presence of YB-1 as well as trans-PARylation of YB-1 are greatly affected by the type of damaged DNA, suggesting that PARP1 activation depends on the formation of a PARP1–YB-1–DNA ternary complex. An unstructured C-terminal part of YB-1 involved in an interaction with PAR behaves similarly to full-length YB-1, indicating that both DNA and PAR binding are involved in the stimulation of PARP1 activity by YB-1. Thus, YB-1 is likely linked to the regulation of PARylation events in cells via an interaction with PAR and damaged DNA.

scholarly journals Nuclear Receptor Binding Protein 2 Is Downregulated in Medulloblastoma, and Reduces Tumor Cell Survival upon Overexpression

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1483
Author(s):  
Anqi Xiong ◽  
Ananya Roy ◽  
Argyris Spyrou ◽  
Holger Weishaupt ◽  
Voichita D. Marinescu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Nuclear Receptor ◽  
Receptor Binding ◽  
Growth Regulation ◽  
Binding Protein ◽  
Histone Deacetylation ◽  
Adult Brain ◽  
Tissue Array ◽  
Receptor Binding Protein

Pseudokinases, comprising 10% of the human kinome, are emerging as regulators of canonical kinases and their functions are starting to be defined. We previously identified the pseudokinase Nuclear Receptor Binding Protein 2 (NRBP2) in a screen for genes regulated during neural differentiation. During mouse brain development, NRBP2 is expressed in the cerebellum, and in the adult brain, mainly confined to specific neuronal populations. To study the role of NRBP2 in brain tumors, we stained a brain tumor tissue array for NRPB2, and find its expression to be low, or absent, in a majority of the tumors. This includes medulloblastoma (MB), a pediatric tumor of the cerebellum. Using database mining of published MB data sets, we also find that NRBP2 is expressed at a lower level in MB than in the normal cerebellum. Recent studies indicate that MB exhibits frequent epigenetic alternations and we therefore treated MB cell lines with drugs inhibiting DNA methylation or histone deacetylation, which leads to an upregulation of NRBP2 mRNA expression, showing that it is under epigenetic regulation in cultured MB cells. Furthermore, forced overexpression of NRBP2 in MB cell lines causes a dramatic decrease in cell numbers, increased cell death, impaired cell migration and inhibited cell invasion in vitro. Taken together, our data indicate that downregulation of NRBP2 may be a feature by which MB cells escape growth regulation.

Stimulation of Ki-ras Ribozyme Activity by RNA Binding Protein, NCp7, in Vitro and in Pancreatic Tumor Cell Line, Capan 1

1994 ◽  
Vol 733 (1 Molecular and) ◽  
pp. 113-121 ◽  
Author(s):  
KARIN MOELLING ◽  
GERD MUELLER ◽  
JENS DANNULL ◽  
CHRISTOPH REUSS ◽  
PETER BEIMLING ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Pancreatic Tumor ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Tumor Cell Line ◽  
Pancreatic Tumor Cell ◽  
Stimulation Of

scholarly journals Genome-Wide DNA Methylation and Transcriptome Analyses Reveal Epigenetic and Genetic Mechanisms Underlying Sex Maintenance of Adult Chinese Alligator

2021 ◽  
Vol 12 ◽  
Author(s):  
Jian-Qing Lin ◽  
Jun Yu ◽  
Li Sun ◽  
Sheng-Guo Fang
Keyword(s):  
Dna Methylation ◽  
Steroid Hormone ◽  
Expression Patterns ◽  
Gonadal Development ◽  
Epigenetic Mechanisms ◽  
Sequencing Data ◽  
Steroid Hormone Biosynthesis ◽  
Bisulfite Sequencing Data ◽  
Hormone Biosynthesis ◽  
Oocyte Meiotic Maturation

The sexes of Chinese alligators are determined during embryonic development and remain fixed thereafter. In this study, we investigated the genetic and epigenetic mechanisms underlying sex maintenance in Chinese alligators through RNA sequencing and bisulfite sequencing data analyses of the adult gonads. We identified the genes and pathways (e. g., DMRT1-SOX9-AMH pathway for males and oocyte meiotic maturation pathway for females) involved in male and female sex maintenance and gonadal development of adult Chinese alligators. In contrast to their expression patterns in the embryo, both DMRT1 and the steroid hormone biosynthesis related genes showed a male-biased expression in adult gonads. The overall DNA methylation density and level were higher in testes than in ovaries. Hypermethylation in the gene bodies enhanced the expression of male-biased genes (such as DMRT1-SOX9-AMH and steroid hormone biosynthesis related genes) in the testis, as opposed to the normalization of gene expression. Our results provide insights into the genetic and epigenetic mechanisms underlying sex maintenance in adult Chinese alligators, and are expected to contribute to the development of scientific programs for the successful conservation of this endangered species.

The inter-talk between Mycobacterium tuberculosis and the epigenetic mechanisms

Epigenomics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 455-469
Author(s):  
Samira Tarashi ◽  
Sara Ahmadi Badi ◽  
Arfa Moshiri ◽  
Nayereh Ebrahimzadeh ◽  
Abolfazl Fateh ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Control Strategy ◽  
Epigenetic Mechanisms ◽  
Human History ◽  
Cellular Processes ◽  
Efficient Control ◽  
Protective Strategy ◽  
Regulate Gene

Epigenetics regulate gene function without any alteration in the DNA sequence. The epigenetics represent one of the most important regulators in different cellular processes and have initially been developed in microorganisms as a protective strategy. The evaluation of the epigenetic mechanisms is also important in achieving an efficient control strategy in tuberculosis (TB). TB is one of the most significant epidemiological concerns in human history. Despite several in vivo and in vitro studies that have evaluated different epigenetic modifications in TB, many aspects of the association between epigenetics and TB are not fully understood. The current paper is aimed at reviewing our knowledge on histone modifications and DNA methylation modifications, as well as miRNAs regulation in TB.

Differential stimulation of capped mRNA translation in vitro by cap binding protein

Nature ◽  
1980 ◽  
Vol 285 (5763) ◽  
pp. 331-333 ◽  
Author(s):  
N. Sonenberg ◽  
H. Trachsel ◽  
S. Hecht ◽  
A. J. Shatkin
Keyword(s):  
Binding Protein ◽  
Mrna Translation ◽  
Stimulation Of

scholarly journals In Vitro Methylation of theBsuRI (5′-GGCC-3′) Sites in the E2a Region of Adenovirus Type 2 DNA Does Not Affect Expression inXenopus laevisOocytes

1982 ◽  
Vol 2 (12) ◽  
pp. 1574-1580 ◽  
Author(s):  
Lily Vardimon ◽  
Ursula Günthert ◽  
Walter Doerfler
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dna Binding ◽  
Cell Lines ◽  
Control Region ◽  
Binding Protein ◽  
Adenovirus Type ◽  
Dna Binding Protein

The early region 2a (E2a) of adenovirus type 2 (Ad2) DNA codes for a 72,000-dalton DNA-binding protein and is expressed in the Ad2-transformed hamster cell line HE1 but not in cell lines HE2 and HE3 (H. Esche, J. Virol.41:1076-1082, 1982; K. Johansson et al., J. Virol.27:628-639, 1978). An inverse correlation between DNA methylation at the 5′-CCGG-3′ sites of the E2a region and of gene expression in these cell lines has been observed (L. Vardimon et al., Nucleic Acids Res.8:2461-2473, 1980). When the cloned E2a region of Ad2 DNA is methylated in vitro at the 5′-CCGG-3′ sites, the gene is not transcribed after being injected into the nuclei ofXenopus laevisoocytes, whereas unmethylated DNA is expressed (L. Vardimon et al., Eur. J. Cell Biol.25:13-15, 1981; L. Vardimon et al., Proc. Natl. Acad. Sci. U.S.A.79:1073-1077, 1982). These data demonstrate that DNA methylation is directly involved in the shut-off of transcription. In the present communication we investigated in detail the control region of the gene for the DNA-binding protein in Ad2-transformed cell lines and showed that the first late control region (map coordinate 72 on the viral DNA) of the E2a region is present in its entirety in cell lines HE1, HE2, and HE3. TheHaeIII sites (5′-GGCC-3′) in the E2a region in all three cell lines were not methylated. When the DNA methyltransferaseBsuRI was used, all 5′-GGCC-3′ sites in the cloned E2a region of Ad2 DNA were methylated in vitro. It was shown that methylation of these sites did not inhibit the expression of this viral gene inX. laevisoocytes. Thus, for methylation to affect gene expression in the E2a region it has to occur at specific sites (e.g., 5′-CCGG-3′) which may be different for other genes.

scholarly journals Nonequilibrium kinetics of a cyclic GMP-binding protein in dictyostelium discoideum

1982 ◽  
Vol 94 (2) ◽  
pp. 271-278 ◽  
Author(s):  
PJM Van Haastert ◽  
H Van Walsum ◽  
FJ Pasveer
Keyword(s):  
Dictyostelium Discoideum ◽  
Cyclic Gmp ◽  
Binding Proteins ◽  
Binding Protein ◽  
Kinetic Constants ◽  
Nonequilibrium Conditions ◽  
Kinetics Of ◽  
Stimulation Of

Chemoattractants added to cells of the cellular slime mold dictyostelium discoideum induce a transient elevation of cyclic GMP levels, with a maximum at 10 s and a recovery of basal levels at approximately 25 s after stimulation. We analyzed the kinetics of an intracellular cGMP binding protein in vitro and in vivo. The cyclic GMP binding protein in vitro at 0 degrees C can be described by its kinetic constants K(1)=2.5 x 10(6) M(- 1)s(-1), k(-1)=3.5 x 10(-3)s(-1), K(d)=1.4 x 10(-9) M, and 3,000 binding sites/cell. In computer simulation experiments the occupancy of the cGMP binding protein was calculated under nonequilibrium conditions by making use of the kinetic constants of the binding protein and of the shape of the cGMP accumulations. These experiments show that under nonequilibrium conditions by making use of the kinetic constants of the binding protein and the shape of the cGMP accumulations. These experiments show that under nonequilibrium conditions the affinity of the binding protein for cGMP is determined by the rate constant of association (k(1)) and not by the dissociation constant (k(d)). Experiments in vivo were performed by stimulation of aggregative cells with the chemoattractant cAMP, which results in a transient cGMP accumulation. At different times after stimulation with various cAMP concentrations, the cells were homogenized and immediately thereafter the number of binding proteins which were not occupied with native cGMP were determined. The results of these experiments in vivo are in good agreement with the results of the computer experiments. This may indicate that: (a) The cGMP binding protein in vivo at 22 degrees C can be described by its kinetic constants: K(1)=4x10(6)M(-1)s(-1) and K(-1)=6x10(-3)s(-1). (b) Binding the cGMP to its binding protein is transient with a maximum at about 20-30 s after chemotactic stimulation, followed by a decay to basal levels, with a half-life of approximately 2 min. (c) The cGMP to its binding proteins get half maximally occupied at a cGMP accumulation of δ[cGMP](10)=2x10(-8) M, which corresponds to an extracellular stimulation of aggregative cells by 10(-10) M cAMP. (d) Since the mean basal cGMP concentration is approximately 2x10(-7) M, the small increase of cGMP cannot be detected accurately. Therefore the absence of a measurable cGMP accumulation does not argue against a cGMP function. (e) There may exist two compartments of cGMP: one contains almost all the cGMP of unstimulated cells, and the other contains cGMP binding proteins and the cGMP which accumulates after chemotactic stimulation. (f) From the kinetics of binding, the cellular responses to the chemoattractant can be divided into two classes: responses which can be mediated by this binding protein (such as light scattering, proton extrusion, PDE induction, and chemotaxis) and responses which cannot be (solely) mediated by this binding protein such as rlay, refractoriness, phospholipids methylation, and protein methylation.

Modification of hematopoietic stem cell fate by 5aza 2′deoxycytidine and trichostatin A

Blood ◽  
2004 ◽  
Vol 103 (11) ◽  
pp. 4102-4110 ◽  
Author(s):  
Mohammed Milhem ◽  
Nadim Mahmud ◽  
Donald Lavelle ◽  
Hiroto Araki ◽  
Joseph DeSimone ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Fate ◽  
Trichostatin A ◽  
Histone Deacetylation ◽  
Proliferative Potential ◽  
Phenotypic Properties ◽  
Hematopoietic Stem ◽  
Immunodeficient Mice ◽  
Cd34 Cells

Abstract Efforts to change the fate of human hematopoietic stem cells (HSCs) and progenitor cells (HPCs) in vitro have met with limited success. We hypothesized that previously utilized in vitro conditions might result in silencing of genes required for the maintenance of primitive HSCs/HPCs. DNA methylation and histone deacetylation are components of an epigenetic program that regulates gene expression. Using pharmacologic agents in vitro that might possibly interfere with DNA methylation and histone deacetylation, we attempted to maintain and expand cells with phenotypic and functional characteristics of primitive HSCs/HPCs. Human marrow CD34+ cells were exposed to a cytokine cocktail favoring differentiation in combination with 5aza 2′deoxycytidine (5azaD) and trichostatin A (TSA), resulting in a significant expansion of a subset of CD34+ cells that possessed phenotypic properties as well as the proliferative potential characteristic of primitive HSCs/HPCs. In addition, 5azaD- and TSA-pretreated cells but not the CD34+ cells exposed to cytokines alone retained the ability to repopulate immunodeficient mice. Our findings demonstrate that 5azaD and TSA can be used to alter the fate of primitive HSCs/HPCs during in vitro culture.

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