17β-Estradiol-Induced Regulation of the Novel 5-HT1A-Related Transcription Factors NUDR and Freud-1 in SH SY5Y Cells

The regulatory region of the neuronal nicotinic acetylcholine (nACh) receptor α2 subunit gene is activated by the Brn-3b POU family transcription factor but not by the closely related factors Brn-3a and Brn-3c. This pattern of regulation has not previously been observed for other neuronally expressed genes, several of which, such as those encoding α-internexin or SNAP-25, are activated by Brn-3a and Brn-3c but repressed by Brn-3b. The α3 nACh receptor subunit gene is also shown to be activated by Brn-3a but is repressed by Brn-3b and Brn-3c. In contrast, the Brn-3 POU family transcription factors have no effects on either the α7 or β4 nACh receptor subunit genes. The actions of Brn-3b on the α2 subunit are thus in contrast to the inhibitory actions of Brn-3b on several promoters that are activated by Brn-3a. The different actions of the Brn-3 POU factors on the range of nACh receptor genes tested suggests that the novel stimulation of the α2 subunit by Brn-3b is specific to this subunit and not a general feature of nACh receptor genes.

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Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes

Endocrinology ◽

10.1210/endocr/bqaa127 ◽

2020 ◽

Vol 161 (9) ◽

Cited By ~ 12

Author(s):

Franck Mauvais-Jarvis ◽

Sabra L Klein ◽

Ellis R Levin

Keyword(s):

Immune Response ◽

Distress Syndrome ◽

Immune Dysregulation ◽

Innate Immune ◽

The Novel ◽

Cytokine Storm ◽

Inflammatory Infiltration ◽

Biological Sex ◽

17Β Estradiol ◽

Novel Coronavirus

Abstract Severe outcomes and death from the novel coronavirus disease 2019 (COVID-19) appear to be characterized by an exaggerated immune response with hypercytokinemia leading to inflammatory infiltration of the lungs and acute respiratory distress syndrome. Risk of severe COVID-19 outcomes is consistently lower in women than men worldwide, suggesting that female biological sex is instrumental in protection. This mini-review discusses the immunomodulatory and anti-inflammatory actions of high physiological concentrations of the steroids 17β-estradiol (E2) and progesterone (P4). We review how E2 and P4 favor a state of decreased innate immune inflammatory response while enhancing immune tolerance and antibody production. We discuss how the combination of E2 and P4 may improve the immune dysregulation that leads to the COVID-19 cytokine storm. It is intended to stimulate novel consideration of the biological forces that are protective in women compared to men, and to therapeutically harness these factors to mitigate COVID-19 morbidity and mortality.

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Functional Significance of Nuclear Estrogen Receptor Subtypes in the Liver of Goldfish

Endocrinology ◽

10.1210/en.2009-1447 ◽

2010 ◽

Vol 151 (4) ◽

pp. 1668-1676 ◽

Cited By ~ 86

Author(s):

Erik R. Nelson ◽

Hamid R. Habibi

Keyword(s):

Strong Support ◽

Somatic Growth ◽

Egg Yolk ◽

Receptor Subtypes ◽

The Novel ◽

Functional Roles ◽

Knock Down ◽

Functional Involvement ◽

17Β Estradiol ◽

Nuclear Estrogen Receptor

Estrogens work by binding to and activating specific estrogen receptors (ERs). Although mammals have two major nuclear ER subtypes (ERα and ERβ), three subtypes have been shown in teleost fish (ERα, ERβ-I, and ERβ-II). 17β-Estradiol stimulates the production of an egg yolk precursor protein (vitellogenin) in the liver of oviparous species, including the goldfish. However, the functional involvement of the ER subtypes in this process is not fully understood. Here, using primary goldfish hepatocytes, we test the hypothesis that all three ER subtypes are functionally involved in the liver of goldfish by using RNA interference to specifically knock-down the different ER subtypes. The results suggest that ERα is induced by estradiol through activation of the ERβ subtypes. This induction serves to sensitize the liver to further stimulation by estradiol. The knock-down results were supported by use of ER subtype specific antagonists. Sensitization by up-regulation of ERα is likely to be important for seasonal spawners such as goldfish, to bring about a change from somatic growth to reproductive development, and vitellogenesis. The novel data presented in this study provide strong support for the hypothesis that the goldfish ER subtypes play functional roles in the regulation of vitellogenin and ERα and provide a framework for the better understanding of ER signaling in fish and other vertebrates.

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Common transcriptional programme of liver fibrosis in mouse genetic models and humans

10.1101/2020.11.02.364901 ◽

2020 ◽

Author(s):

Kaja Blagotinšek Cokan ◽

Žiga Urlep ◽

Miha Moškon ◽

Miha Mraz ◽

Xiang Y. Kong ◽

...

Keyword(s):

Transcription Factors ◽

Liver Fibrosis ◽

Metabolic Diseases ◽

Genetic Models ◽

Disease Stage ◽

The Novel ◽

Alcoholic Fatty Liver ◽

Metabolic Modelling ◽

Cancer Pathways ◽

Genome Scale

AbstractMultifactorial metabolic diseases, such as non-alcoholic fatty liver disease, are a major burden of modern societies and frequently present with no clearly defined molecular biomarkers. Herein we used systems medicine approaches to decipher signatures of liver fibrosis in mouse models with malfunction in genes from unrelated biological pathways. Enrichment analyses of KEGG, Reactome and TRANSFAC databases complemented with genome-scale metabolic modelling revealed fibrotic signatures highly similar to liver pathologies in humans. The diverse genetic models of liver fibrosis exposed a common transcriptional programme with activated ERα signalling, and a network of interactions between regulators of lipid metabolism and transcription factors from cancer pathways and immune system. The novel hallmarks of fibrosis are downregulated lipid pathways, including fatty acid, bile acid, and steroid hormone metabolism. Moreover, distinct metabolic subtypes of liver fibrosis were proposed, supported by unique enrichment of transcription factors based on the type of insult, disease stage, or sex.

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Novel ChIP-seq simulating program with superior versatility: isChIP

Briefings in Bioinformatics ◽

10.1093/bib/bbaa352 ◽

2020 ◽

Author(s):

Tatiana Subkhankulova ◽

Fedor Naumenko ◽

Oleg E Tolmachov ◽

Yuriy L Orlov

Keyword(s):

Transcription Factors ◽

The Novel ◽

Chip Sequencing ◽

Protein Factor ◽

Wide Range ◽

Computational Data ◽

Associated Proteins ◽

Wet Lab ◽

Sequencing Platforms ◽

Core Problem

Abstract Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) is recognized as an extremely powerful tool to study the interaction of numerous transcription factors and other chromatin-associated proteins with DNA. The core problem in the optimization of ChIP-seq protocol and the following computational data analysis is that a ‘true’ pattern of binding events for a given protein factor is unknown. Computer simulation of the ChIP-seq process based on ‘a-priory known binding template’ can contribute to a drastically reduce the number of wet lab experiments and finally help achieve radical optimization of the entire processing pipeline. We present a newly developed ChIP-sequencing simulation algorithm implemented in the novel software, in silico ChIP-seq (isChIP). We demonstrate that isChIP closely approximates real ChIP-seq protocols and is able to model data similar to those obtained from experimental sequencing. We validated isChIP using publicly available datasets generated for well-characterized transcription factors Oct4 and Sox2. Although the novel software is compatible with the Illumina protocols by default, it can also successfully perform simulations with a number of alternative sequencing platforms such as Roche454, Ion Torrent and SOLiD as well as model ChIP -Exo. The versatility of isChIP was demonstrated through modelling a wide range of binding events, including those of transcription factors and chromatin modifiers. We also performed a comparative analysis against a few existing ChIP-seq simulators and showed the fundamental superiority of our model. Due to its ability to utilize known binding templates, isChIP can potentially be employed to help investigators choose the most appropriate analytical software through benchmarking of available ChIP-seq programs and optimize the experimental parameters of ChIP-seq protocol. isChIP software is freely available at https://github.com/fnaumenko/isChIP.

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Upstream stimulatory factors stimulate transcription through E-box motifs in the PF4 gene in megakaryocytes

Blood ◽

10.1182/blood-2003-09-3107 ◽

2004 ◽

Vol 104 (7) ◽

pp. 2027-2034 ◽

Cited By ~ 16

Author(s):

Yoshiaki Okada ◽

Eri Matsuura ◽

Zenzaburo Tozuka ◽

Ryohei Nagai ◽

Ayako Watanabe ◽

...

Keyword(s):

Transcription Factors ◽

Regulatory Element ◽

The Novel ◽

Upstream Stimulatory Factor ◽

Platelet Factor ◽

Cd34 Cells ◽

E Box ◽

Hel Cells ◽

B Cell Leukemia ◽

Stimulatory Factor

Abstract Platelet factor 4 (PF4) is expressed during megakaryocytic differentiation. We previously demonstrated that the homeodomain proteins (myeloid ecotropic integra tion site 1 [MEIS1], Pbx-regulating protein 1 [PREP1], and pre-B-cell leukemia transcription factors [PBXs]) bind to the novel regulatory element tandem repeat of MEIS1 binding element [TME] and transactivate the rat PF4 promoter. In the present study, we investigated and identified other TME binding proteins in megakaryocytic HEL cells using mass spectrometry. Among identified proteins, we focused on upstream stimulatory factor (USF1) and USF2 and investigated their effects on the PF4 promoter. USF1 and 2 bound to the E-box motif in the TME and strongly transactivated the PF4 promoter. Furthermore, physiologic bindings of USF1 and 2 to the TME in rat megakaryocytes were demonstrated by the chromatin immunoprecipitation (ChIP) assay. Interestingly, the E-box motif in the TME was conserved in TME-like sequences of both the human and mouse PF4 promoters. USF1 and 2 also bound to the human TME-like sequence and transactivated the human PF4 promoter. Expressions of USF1 and 2 were detected by reverse-transcriptase–polymerase chain reaction (RT-PCR) in the human megakaryocytes derived from CD34+ cells. Thus, these studies demonstrate that the novel TME binding transcription factors, USF1 and 2, transactivate rat and human PF4 promoters and may play an important role in megakaryocytic gene expression.

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Activation of MAPKs by 1α,25(OH)2-Vitamin D3 and 17β-estradiol in skeletal muscle cells leads to phosphorylation of Elk-1 and CREB transcription factors

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2006.11.005 ◽

2007 ◽

Vol 103 (3-5) ◽

pp. 462-466 ◽

Cited By ~ 28

Author(s):

Ana C. Ronda ◽

Claudia Buitrago ◽

Andrea Colicheo ◽

Ana R. de Boland ◽

Emilio Roldán ◽

...

Keyword(s):

Skeletal Muscle ◽

Transcription Factors ◽

Vitamin D3 ◽

Muscle Cells ◽

Skeletal Muscle Cells ◽

17Β Estradiol

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Role of SP transcription factors in hormone-dependent modulation of genes in MCF-7 breast cancer cells: microarray and RNA interference studies

Journal of Molecular Endocrinology ◽

10.1677/jme-08-0088 ◽

2008 ◽

Vol 42 (1) ◽

pp. 19-33 ◽

Cited By ~ 13

Author(s):

Fei Wu ◽

Ivan Ivanov ◽

Rui Xu ◽

Stephen Safe

Keyword(s):

Transcription Factors ◽

Rna Interference ◽

Estrogen Receptor Α ◽

Independent Analysis ◽

17Β Estradiol ◽

Specificity Protein ◽

Interference Studies ◽

Sp Transcription Factors ◽

Mcf 7

17β-Estradiol (E2) binds estrogen receptor α (ESR1) in MCF-7 cells and increases cell proliferation and survival through induction or repression of multiple genes. ESR1 interactions with DNA-bound specificity protein (SP) transcription factors is a nonclassical genomic estrogenic pathway and the role of SP transcription factors in mediating hormone-dependent activation or repression of genes in MCF-7 cells was investigated by microarrays and RNA interference. MCF-7 cells were transfected with a nonspecific oligonucleotide or a cocktail of small inhibitory RNAs (iSP), which knockdown SP1, SP3, and SP4 proteins, and treated with dimethylsulfoxide or 10 nM E2 for 6 h. E2 induced 62 and repressed 134 genes and the induction or repression was reversed in ∼62% of the genes in cells transfected with iSP (ESR1/SP dependent), whereas hormonal activation or repression of the remaining genes was unaffected by iSP (SP independent). Analysis of the ESR1/SP-dependent and SP-independent genes showed minimal overlap with respect to the GO terms (functional processes) in genes induced or repressed, suggesting that the different genomic pathways may contribute independently to the hormone-induced phenotype in MCF-7 cells.

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bZIP Transcription Factors in the Oomycete Phytophthora infestans with Novel DNA-Binding Domains Are Involved in Defense against Oxidative Stress

Eukaryotic Cell ◽

10.1128/ec.00141-13 ◽

2013 ◽

Vol 12 (10) ◽

pp. 1403-1412 ◽

Cited By ~ 26

Author(s):

Heber Gamboa-Meléndez ◽

Apolonio I. Huerta ◽

Howard S. Judelson

Keyword(s):

Transcription Factors ◽

Dna Binding ◽

Phytophthora Infestans ◽

Stress Responses ◽

Leucine Zipper ◽

Stable Gene ◽

Mrna Levels ◽

The Novel ◽

Basic Leucine Zipper ◽

Content Type

ABSTRACT Transcription factors of the basic leucine zipper (bZIP) family control development and stress responses in eukaryotes. To date, only one bZIP has been described in any oomycete; oomycetes are members of the stramenopile kingdom. In this study, we describe the identification of 38 bZIPs from the Phytophthora infestans genome. Half contain novel substitutions in the DNA-binding domain at a site that in other eukaryotes is reported to always be Asn. Interspecific comparisons indicated that the novel substitutions (usually Cys, but also Val and Tyr) arose after oomycetes diverged from other stramenopiles. About two-thirds of P. infestans bZIPs show dynamic changes in mRNA levels during the life cycle, with many of the genes being upregulated in sporangia, zoospores, or germinated zoospore cysts. One bZIP with the novel Cys substitution was shown to reside in the nucleus throughout growth and development. Using stable gene silencing, the functions of eight bZIPs with the Cys substitution were tested. All but one were found to play roles in protecting P. infestans from hydrogen peroxide-induced injury, and it is proposed that the novel Cys substitution serves as a redox sensor. A ninth bZIP lacking the novel Asn-to-Cys substitution, but having Cys nearby, was also shown through silencing to contribute to defense against peroxide. Little effect on asexual development, plant pathogenesis, or resistance to osmotic stress was observed in transformants silenced for any of the nine bZIPs.

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