Mechanism of Steroid Hormone Action: In Vitro Control of Gene Expression in Chick Oviduct Chromatin by Purified Steroid Receptor Complexes

1976 ◽  
pp. 530-556
Author(s):  
R. J. Schwartz ◽  
W. T. Schrader ◽  
B. W. O’Malley
Keyword(s):  
Gene Expression ◽  
Steroid Hormone ◽  
Steroid Receptor ◽  
Hormone Action ◽  
Control Of Gene Expression ◽  
Receptor Complexes

scholarly journals The Mycobacterium tuberculosis sRNA F6 regulates expression of groEL/S

2020 ◽  
Author(s):  
Joanna Houghton ◽  
Angela Rodgers ◽  
Graham Rose ◽  
Kristine B. Arnvig
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Small Rnas ◽  
Transcriptional Control ◽  
Cold Shock ◽  
Control Of Gene Expression ◽  
Rna Biology ◽  
Mouse Model Of Infection

ABSTRACTAlmost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of post-transcriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA, F6, and show it to be dependent on SigF for expression and significantly induced during in vitro starvation and in a mouse model of infection. However, we found no evidence of attenuation of a ΔF6 strain within the first 20 weeks of infection. A further exploration of F6 using in vitro models of infection suggests a role for F6 as a highly specific regulator of the heat shock repressor, HrcA. Our results point towards a role for F6 during periods of low metabolic activity similar to cold shock and associated with nutrient starvation such as that found in human granulomas in later stages of infection.

scholarly journals Nuclear acceptor sites for androgen-receptor complexes in seminal-vesicle epithelium

1980 ◽  
Vol 192 (1) ◽  
pp. 41-47 ◽  
Author(s):  
M J Weinberger ◽  
C M Veneziale
Keyword(s):  
Seminal Vesicle ◽  
Nuclear Dna ◽  
Steroid Receptor ◽  
Assay Method ◽  
Scatchard Analysis ◽  
Receptor Complex ◽  
Receptor Complexes ◽  
Constant Slope

An assay method in vitro was developed and applied to quantify acceptor binding of steroid-receptor complexes in nuclei from isolated epithelium of guinea-pig seminal vesicle. Steroid-receptor complex prepared from 1-day-castrated animals was incubated with purified nuclei from 1-28 day-castrated animals in a medium containing 0.15 M-KCl. Free and bound steroid-receptor complexes were measured and the data were submitted to Scatchard analysis. With nuclei from 1-day-castrated animals the Kd for binding of cytosolic [3H]dihydrotestosterone-receptor complexes was found to be 0.83 × 10(-10) M and the capacity for binding was 0.35 pmol/mg of nuclear DNA. Scatchard analysis consistently disclosed only a single line of constant slope and gave the same kinetic constants for nuclei obtained from animals castrated up to 28 days before assay. Administration of 2 mg of dihydrotestosterone, 3 alpha-androstanediol or androsterone or 100 microgram of oestradiol-17 beta 1 h before killing of the 1-day-castrated animals that provided the nuclei resulted in a significant decrease in nuclear acceptor binding of the steroid-receptor complex compared with untreated animals. Thus our assay method disclosed nuclear acceptor sites that may be involved in responses to androgens (and oestrogens) in vivo. We conclude that there is a class of nuclear accept or sites of high affinity and limited capacity that may be occupied by steroid-receptor complexes in vivo.

DEFECTIVE STEROIDAL SYNTHESIS BY ADRENAL TISSUE: THE CONTROL OF GENE EXPRESSION CAUSING LOSS OF ACTIVE STEROIDOGENIC ENZYMES

1974 ◽  
Vol 77 (2) ◽  
pp. 325-336
Author(s):  
K. Williams
Keyword(s):  
Gene Expression ◽  
Adrenal Glands ◽  
Hydroxysteroid Dehydrogenase ◽  
Ascites Cell ◽  
Control Of Gene Expression ◽  
Adrenocortical Hyperplasia ◽  
Normal Human ◽  
Adrenocortical Tumour

ABSTRACT RNA was isolated from normal human adrenal glands and found to cause the formation of Δ5-3β-hydroxysteroid dehydrogenase-isomerase and steroid 21-hydroxylase activities by a Krebs II ascites cell-free protein synthesising system. Although no functional steroid 21-hydroxylase in vivo or in vitro was found in a gland from a patient with virilism due to congenital adrenocortical hyperplasia the RNA would still give steroid 21-hydroxylase-like activity in the protein synthesising system which suggests that the inherited defect was not in the structural gene. Activity could not be induced by RNA from a 'non-functioning' adrenocortical tumour or rat liver.

Cell-specific posttranscriptional regulation of CFTR gene expression via influence of MAPK cascades on 3′UTR part of transcripts

2005 ◽  
Vol 289 (5) ◽  
pp. C1240-C1250 ◽  
Author(s):  
Maryvonne Baudouin-Legros ◽  
Alexandre Hinzpeter ◽  
Amandine Jaulmes ◽  
Franck Brouillard ◽  
Bruno Costes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Posttranscriptional Regulation ◽  
P38 Map Kinase ◽  
Cftr Gene ◽  
Control Of Gene Expression ◽  
Cytosolic Proteins ◽  
Tnf Α ◽  
Ht 29

Expression of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene, which contains the mutations responsible for CF, is regulated by cytokines (TNF-α and IL-1β) in a cell-specific manner. TNF-α decreases CFTR mRNA in human colon cell lines (HT-29), but not in pulmonary cell lines (Calu-3), and IL-1β increases it only in Calu-3 cells. We looked for the cytokine-induced posttranscriptional regulation of CFTR gene expression and studied the modulation of CFTR mRNA stability linked to its 3′ untranslated sequence (3′UTR) in HT-29 and Calu-3 cells. The stability of CFTR mRNA was analyzed by Northern blot after in vitro incubation of total RNAs from CFTR-expressing cells with cytosolic proteins extracted from control or cytokine-treated HT-29 and Calu-3 cells. CFTR mRNA was degraded only by extracts of TNF-α-treated HT-29 cells and not by cytosolic proteins from untreated or IL-1β-treated HT-29 cells. In contrast, extracts of untreated Calu-3 cells enhanced CFTR mRNA degradation, and IL-1β treatment inhibited this; TNF-α had no significant effect. The 3′UTR part of CFTR mRNA was found to be required for this posttranscriptional regulation. The 5′ part of the 3′UTR (the 217 first bases), which contains two AUUUA sequences, was implicated in CFTR mRNA destabilization and the following 136 bases, containing several C-repeats in U-rich environment, in its protection. The proteins, which reacted with the U- and C-repeats of CFTR mRNA 3′UTR, were mainly controlled by stimulation of the p42/p44 and p38 MAP kinase cascades with interaction between these pathways. This posttranscriptional control of gene expression is a common feature of CFTR and many proteins of inflammation.

scholarly journals Attenuation of Glucocorticoid Signaling through Targeted Degradation of p300 via the 26S Proteasome Pathway

2002 ◽  
Vol 16 (12) ◽  
pp. 2819-2827 ◽  
Author(s):  
Qiao Li ◽  
Anna Su ◽  
Jihong Chen ◽  
Yvonne A. Lefebvre ◽  
Robert J. G. Haché
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptor ◽  
Sodium Butyrate ◽  
Steroid Receptor ◽  
26S Proteasome ◽  
Regulatory Control ◽  
Specific Gene ◽  
Control Of Gene Expression ◽  
Steroid Receptor Coactivator ◽  
Proteasome Pathway

Abstract The effects of acetylation on gene expression are complex, with changes in chromatin accessibility intermingled with direct effects on transcriptional regulators. For the nuclear receptors, both positive and negative effects of acetylation on specific gene transcription have been observed. We report that p300 and steroid receptor coactivator 1 interact transiently with the glucocorticoid receptor and that the acetyltransferase activity of p300 makes an important contribution to glucocorticoid receptor-mediated transcription. Treatment of cells with the deacetylase inhibitor, sodium butyrate, inhibited steroid-induced transcription and altered the transient association of glucocorticoid receptor with p300 and steroid receptor coactivator 1. Additionally, sustained sodium butyrate treatment induced the degradation of p300 through the 26S proteasome pathway. Treatment with the proteasome inhibitor MG132 restored both the level of p300 protein and the transcriptional response to steroid over 20 h of treatment. These results reveal new levels for the regulatory control of gene expression by acetylation and suggest feedback control on p300 activity.

scholarly journals Progressive lengthening of 3′ untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development

2009 ◽  
Vol 106 (17) ◽  
pp. 7028-7033 ◽  
Author(s):  
Zhe Ji ◽  
Ju Youn Lee ◽  
Zhenhua Pan ◽  
Bingjun Jiang ◽  
Bin Tian
Keyword(s):  
Gene Expression ◽  
Embryonic Development ◽  
Posttranscriptional Regulation ◽  
Regulation Of Gene Expression ◽  
Alternative Polyadenylation ◽  
Untranslated Regions ◽  
C2c12 Myoblast ◽  
Control Of Gene Expression ◽  
Differentiation And Proliferation

The 3′ untranslated regions (3′ UTRs) of mRNAs containcis-acting elements for posttranscriptional regulation of gene expression. Here, we report that mouse genes tend to express mRNAs with longer 3′ UTRs as embryonic development progresses. This global regulation is controlled by alternative polyadenylation and coordinates with initiation of organogenesis and aspects of embryonic development, including morphogenesis, differentiation, and proliferation. Using myogenesis of C2C12 myoblast cells as a model, we recapitulated this process in vitro and found that 3′ UTR lengthening is likely caused by weakening of mRNA polyadenylation activity. Because alternative 3′ UTR sequences are typically longer and have higher AU content than constitutive ones, our results suggest that lengthening of 3′ UTR can significantly augment posttranscriptional control of gene expression during embryonic development, such as microRNA-mediated regulation.

scholarly journals Intrusion of a DNA Repair Protein in the RNome World: Is This the Beginning of a New Era?

2009 ◽  
Vol 30 (2) ◽  
pp. 366-371 ◽  
Author(s):  
Gianluca Tell ◽  
David M. Wilson ◽  
Chow H. Lee
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Mrna Level ◽  
Rna Metabolism ◽  
Coding Region ◽  
Control Of Gene Expression ◽  
Dna And Rna ◽  
New Findings

ABSTRACT Apurinic/apyrimidinic endonuclease 1 (APE1), an essential protein in mammals, is known to be involved in base excision DNA repair, acting as the major abasic endonuclease; the protein also functions as a redox coactivator of several transcription factors that regulate gene expression. Recent findings highlight a novel role for APE1 in RNA metabolism. The new findings are as follows: (i) APE1 interacts with rRNA and ribosome processing protein NPM1 within the nucleolus; (ii) APE1 interacts with proteins involved in ribosome assembly (i.e., RLA0, RSSA) and RNA maturation (i.e., PRP19, MEP50) within the cytoplasm; (iii) APE1 cleaves abasic RNA; and (iv) APE1 cleaves a specific coding region of c-myc mRNA in vitro and influences c-myc mRNA level and half-life in cells. Such findings on the role of APE1 in the posttranscriptional control of gene expression could explain its ability to influence diverse biological processes and its relocalization to cytoplasmic compartments in some tissues and tumors. In addition, we propose that APE1 serves as a “cleansing” factor for oxidatively damaged abasic RNA, establishing a novel connection between DNA and RNA surveillance mechanisms. In this review, we introduce questions and speculations concerning the role of APE1 in RNA metabolism and discuss the implications of these findings in a broader evolutionary context.

The role of 5a-reduction in steroid hormone physiology

2001 ◽  
Vol 13 (8) ◽  
pp. 673 ◽  
Author(s):  
Jean D. Wilson
Keyword(s):  
Essential Role ◽  
Steroid Hormone ◽  
Urogenital Sinus ◽  
Receptor Complex ◽  
Hormone Action ◽  
Steroid Molecule ◽  
Male Development ◽  
Broad Specificity

A role for 5α-reduction in androgen physiology was first established with the recognition that dihydrotestosterone, the 5α-reduced metabolite of testosterone, is formed in many androgen target tissues, binds to the androgen receptor with greater affinity than testosterone, and plays an essential role in virilization of the urogenital sinus and urogenital tubercle during male development. Two 5α-reductases perform this reaction, and both isoenzymes utilize NADPH as cofactor and have broad specificity for steroids containing a Δ4, 3-keto configuration. 5α-Reduction, which is essentially irreversible, flattens the steroid molecule because of altered relation of the A and B rings, and stabilizes the hormone–receptor complex. Studies involving in vitro reporter gene assays and intact mice in which both isoenzymes are disrupted, indicate that the fundamental effect of dihydrotestosterone formation is to amplify hormonal signals that can be mediated by testosterone at higher concentrations. 5α-Reduction also plays a role in the action of other steroid hormones, including the plant growth hormone, brassinolide, the boar pheromones, androstanol and androstenol, progesterone (in some species), and, possibly, aldosterone and cortisol. The fact that the reaction is important in plants and animals implies a fundamental role in steroid hormone action.

scholarly journals The RNA–RNA base pairing potential of human Dicer and Ago2 proteins

2019 ◽  
Vol 77 (16) ◽  
pp. 3231-3244 ◽  
Author(s):  
Maria Pokornowska ◽  
Marek C. Milewski ◽  
Kinga Ciechanowska ◽  
Agnieszka Szczepańska ◽  
Marta Wojnicka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Rna Structure ◽  
Small Interfering Rnas ◽  
Base Pairing ◽  
Complementary Sequence ◽  
Control Of Gene Expression ◽  
Complementary Sequences

Abstract The ribonuclease Dicer produces microRNAs (miRNAs) and small interfering RNAs that are handed over to Ago proteins to control gene expression by targeting complementary sequences within transcripts. Interestingly, a growing number of reports have demonstrated that the activity of Dicer may extend beyond the biogenesis of small regulatory RNAs. Among them, a report from our latest studies revealed that human Dicer facilitates base pairing of complementary sequences present in two nucleic acids, thus acting as a nucleic acid annealer. Accordingly, in this manuscript, we address how RNA structure influences the annealing activity of human Dicer. We show that Dicer supports hybridization between a small RNA and a complementary sequence of a longer RNA in vitro, even when both complementary sequences are trapped within secondary structures. Moreover, we show that under applied conditions, human Ago2, a core component of RNA-induced silencing complex, displays very limited annealing activity. Based on the available data from new-generation sequencing experiments regarding the RNA pool bound to Dicer in vivo, we show that multiple Dicer-binding sites within mRNAs also contain miRNA targets. Subsequently, we demonstrate in vitro that Dicer but not Ago2 can anneal miRNA to its target present within mRNA. We hypothesize that not all miRNA duplexes are handed over to Ago proteins. Instead, miRNA-Dicer complexes could target specific sequences within transcripts and either compete or cooperate for binding sites with miRNA-Ago complexes. Thus, not only Ago but also Dicer might be directly involved in the posttranscriptional control of gene expression.

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