scholarly journals ADP-ribose derived Nuclear ATP is Required for Chromatin Remodeling and Hormonal Gene Regulation (97 charact)

2014 ◽  
Author(s):  
Roni H. G. Wright ◽  
Francois LeDily ◽  
Daniel Soronellas ◽  
Andy Pohl ◽  
Jaume Bonet ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Gene Regulation ◽  
Chromatin Remodeling ◽  
Atp Synthesis ◽  
List Type ◽  
Cell Nuclei ◽  
Energy Consuming ◽  
Regulation Changes ◽  
Nuclear Processes ◽  
Hydrolysis Of

Highlights–Hormonal gene regulation requires synthesis of PAR and its degradation to ADP-ribose by PARG–ADP-ribose is converted to ATP in the cell nuclei by hormone-activated NUDIX5/NUDT5–Blocking nuclear ATP formation precludes hormone-induced chromatin remodeling, gene regulation and cell proliferationSummaryKey nuclear processes in eukaryotes including DNA replication or repair and gene regulation require extensive chromatin remodeling catalyzed by energy consuming enzymes. How the energetic demands of such processes are ensured in response to rapid stimuli remains unclear. We have analyzed this question in the context of the massive gene regulation changes induced by progestins in breast cancer cells and found that ATP is generated in the cell nucleus via the hydrolysis of poly-ADP-ribose to ADP-ribose. Nuclear ATP synthesis requires the combined enzymatic activities of PARP1, PARG and NUDIX5/NUDT5. Although initiated via mitochondrial derived ATP, the nuclear source of ATP is essential for hormone induced chromatin remodeling, gene regulation and cell proliferation and may also participate in DNA repair. This novel pathway reveals exciting avenues of research for drug development.

INDIREKTE PAPIERCHROMATOGRAPHISCHE METHODE ZUR BESTIMMUNG DER HARNOESTROGENE

1961 ◽  
Vol 38 (4) ◽  
pp. 545-562 ◽  
Author(s):  
L. Kecskés ◽  
F. Mutschler ◽  
I. Glós ◽  
E. Thán ◽  
I. Farkas ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Granulosa Cell ◽  
Iron Content ◽  
List Type ◽  
Granulosa Cell Tumour ◽  
Hydrolysis Of ◽  
Phenol Fraction ◽  
Qualitative Determination

ABSTRACT 1. An indirect paperchromatographic method is described for separating urinary oestrogens; this consists of the following steps: acidic hydrolysis, extraction with ether, dissociation of phenol-fractions with partition between the solvents. Previous purification of phenol fraction with the aid of paperchromatography. The elution of oestrogen containing fractions is followed by acetylation. Oestrogen acetate is isolated by re-chromatography. The chromatogram was developed after hydrolysis of the oestrogens 'in situ' on the paper. The quantity of oestrogens was determined indirectly, by means of an iron-reaction, after the elution of the iron content of the oestrogen spot, which was developed by the Jellinek-reaction. 2. The method described above is satisfactory for determining urinary oestrogen, 17β-oestradiol and oestriol, but could include 16-epioestriol and other oestrogenic metabolites. 3. The sensitivity of the method is 1.3–1.6 μg/24 hours. 4. The quantitative and qualitative determination of urinary oestrogens with the above mentioned method was performed in 50 pregnant and 9 non pregnant women, and also in 2 patients with granulosa cell tumour.

scholarly journals Remodeler Catalyzed Nucleosome Repositioning: Influence of Structure and Stability

2020 ◽  
Vol 22 (1) ◽  
pp. 76
Author(s):  
Aaron Morgan ◽  
Sarah LeGresley ◽  
Christopher Fischer
Keyword(s):  
Free Energy ◽  
Dna Replication ◽  
Recent Work ◽  
Chromatin Remodeling ◽  
Chromatin Structure ◽  
Genetic Information ◽  
Molecular Machines ◽  
Mechanical Work ◽  
Eukaryotic Genome ◽  
Hydrolysis Of

The packaging of the eukaryotic genome into chromatin regulates the storage of genetic information, including the access of the cell’s DNA metabolism machinery. Indeed, since the processes of DNA replication, translation, and repair require access to the underlying DNA, several mechanisms, both active and passive, have evolved by which chromatin structure can be regulated and modified. One mechanism relies upon the function of chromatin remodeling enzymes which couple the free energy obtained from the binding and hydrolysis of ATP to the mechanical work of repositioning and rearranging nucleosomes. Here, we review recent work on the nucleosome mobilization activity of this essential family of molecular machines.

scholarly journals MRG15 Regulates Embryonic Development and Cell Proliferation

2005 ◽  
Vol 25 (8) ◽  
pp. 2924-2937 ◽  
Author(s):  
Kaoru Tominaga ◽  
Bhakti Kirtane ◽  
James G. Jackson ◽  
Yuji Ikeno ◽  
Takayoshi Ikeda ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Embryonic Development ◽  
Chromatin Remodeling ◽  
Histone Deacetylases ◽  
Globin Gene ◽  
Immunohistochemical Analysis ◽  
Wild Type ◽  
Proliferating Cells ◽  
Globin Promoter

ABSTRACT MRG15 is a highly conserved protein, and orthologs exist in organisms from yeast to humans. MRG15 associates with at least two nucleoprotein complexes that include histone acetyltransferases and/or histone deacetylases, suggesting it is involved in chromatin remodeling. To study the role of MRG15 in vivo, we generated knockout mice and determined that the phenotype is embryonic lethal, with embryos and the few stillborn pups exhibiting developmental delay. Immunohistochemical analysis indicates that apoptosis in Mrg15 − / − embryos is not increased compared with wild-type littermates. However, the number of proliferating cells is significantly reduced in various tissues of the smaller null embryos compared with control littermates. Cell proliferation defects are also observed in Mrg15 − / − mouse embryonic fibroblasts. The hearts of the Mrg15 − / − embryos exhibit some features of hypertrophic cardiomyopathy. The increase in size of the cardiomyocytes is most likely a response to decreased growth of the cells. Mrg15 − / − embryos appeared pale, and microarray analysis revealed that α-globin gene expression was decreased in null versus wild-type embryos. We determined by chromatin immunoprecipitation that MRG15 was recruited to the α-globin promoter during dimethyl sulfoxide-induced mouse erythroleukemia cell differentiation. These findings demonstrate that MRG15 has an essential role in embryonic development via chromatin remodeling and transcriptional regulation.

The trithorax group gene osa encodes an ARID-domain protein that genetically interacts with the brahma chromatin-remodeling factor to regulate transcription

Development ◽  
1999 ◽  
Vol 126 (4) ◽  
pp. 733-742 ◽  
Author(s):  
M. Vazquez ◽  
L. Moore ◽  
J.A. Kennison
Keyword(s):  
Gene Regulation ◽  
Chromatin Remodeling ◽  
Homeotic Gene ◽  
Dna Binding Domain ◽  
Atpase Subunit ◽  
Trithorax Group ◽  
Chromatin Remodeling Complex ◽  
P2 Promoter ◽  
Domain Protein ◽  
Arid Domain

The trithorax group gene brahma (brm) encodes the ATPase subunit of a chromatin-remodeling complex involved in homeotic gene regulation. We report here that brm interacts with another trithorax group gene, osa, to regulate the expression of the Antennapedia P2 promoter. Regulation of Antennapedia by BRM and OSA proteins requires sequences 5′ to the P2 promoter. Loss of maternal osa function causes severe segmentation defects, indicating that the function of osa is not limited to homeotic gene regulation. The OSA protein contains an ARID domain, a DNA-binding domain also present in the yeast SWI1 and Drosophila DRI proteins. We propose that the OSA protein may target the BRM complex to Antennapedia and other regulated genes.

Endothelin-A receptor antagonist BQ-610 blocks cigarette smoke-induced mitogenesis in rat airways and vessels

1997 ◽  
Vol 272 (4) ◽  
pp. L614-L618 ◽  
Author(s):  
F. Dadmanesh ◽  
J. L. Wright
Keyword(s):  
Cell Proliferation ◽  
Cigarette Smoke ◽  
Airway Epithelial ◽  
Sprague Dawley ◽  
Cell Nuclei ◽  
Sprague Dawley Rats ◽  
Endothelin A ◽  
Bq 610 ◽  
Air Control ◽  
Wall Components

To ascertain whether endothelin may play a role in cigarette smoke-induced cell proliferation in the airways and arterial vasculature of the lung, we exposed groups of seven Sprague-Dawley rats to either room air (control) plus saline infusion, an intravenous infusion of the selective endothelin A antagonist BQ-610 (control BQ-610), the smoke of 10 cigarettes (smoke only), or the smoke of 10 cigarettes after intravenous BQ-610 infusion (smoke + BQ-610). Cell proliferation was quantified by determining the percentage of cell nuclei labeled by 5-bromo-2'-deoxyuridine. We separately evaluated the cells in the epithelium and wall components of the bronchioles, and endothelium and wall components of the peribronchiolar and perialveolar ductular arteries. We found that cigarette smoke produced significant cell proliferation in the airway epithelium and wall, in the peribronchiolar arterial endothelial compartment, and in both the endothelial and wall compartments of the perialveolar ductular arteries. Pretreatment with BQ-610 reduced the peribronchiolar arterial endothelial and the perialveolar ductular arterial wall proliferation to control lev- els and reduced but did not totally abrogate the smoke-in- duced proliferation of the airway epithelial, airway wall, and perialveolar ductular arterial endothelial compartments. We conclude that cigarette smoke-induced cell proliferation of the airways and pulmonary arterial vessels is at least partially mediated through stimulation of the endothelin-A receptors.

scholarly journals Brahma is essential for Drosophila intestinal stem cell proliferation and regulated by Hippo signaling

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Yunyun Jin ◽  
Jinjin Xu ◽  
Meng-Xin Yin ◽  
Yi Lu ◽  
Lianxin Hu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Chromatin Remodeling ◽  
Intestinal Stem Cells ◽  
Hippo Signaling ◽  
Protein Levels ◽  
Chromatin Remodeling Complex ◽  
Proliferation And Differentiation ◽  
Resistant Form ◽  
Specific Manner ◽  
Transcriptional Complex

Chromatin remodeling processes are among the most important regulatory mechanisms in controlling cell proliferation and regeneration. Drosophila intestinal stem cells (ISCs) exhibit self-renewal potentials, maintain tissue homeostasis, and serve as an excellent model for studying cell growth and regeneration. In this study, we show that Brahma (Brm) chromatin-remodeling complex is required for ISC proliferation and damage-induced midgut regeneration in a lineage-specific manner. ISCs and enteroblasts exhibit high levels of Brm proteins; and without Brm, ISC proliferation and differentiation are impaired. Importantly, the Brm complex participates in ISC proliferation induced by the Scalloped–Yorkie transcriptional complex and that the Hippo (Hpo) signaling pathway directly restricted ISC proliferation by regulating Brm protein levels by inducing caspase-dependent cleavage of Brm. The cleavage resistant form of Brm protein promoted ISC proliferation. Our findings highlighted the importance of Hpo signaling in regulating epigenetic components such as Brm to control downstream transcription and hence ISC proliferation.

scholarly journals FIREcaller: Detecting Frequently Interacting Regions from Hi-C Data

2019 ◽  
Author(s):  
Cheynna Crowley ◽  
Yuchen Yang ◽  
Yunjiang Qiu ◽  
Benxia Hu ◽  
Armen Abnousi ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Spatial Organization ◽  
R Package ◽  
Specific Gene ◽  
List Type ◽  
Cell Type ◽  
R Software ◽  
Computational Tools ◽  
Cell Type Specific ◽  
User Friendly

AbstractHi-C experiments have been widely adopted to study chromatin spatial organization, which plays an essential role in genome function. We have recently identified frequently interacting regions (FIREs) and found that they are closely associated with cell-type-specific gene regulation. However, computational tools for detecting FIREs from Hi-C data are still lacking. In this work, we present FIREcaller, a stand-alone, user-friendly R package for detecting FIREs from Hi-C data. FIREcaller takes raw Hi-C contact matrices as input, performs within-sample and cross-sample normalization, and outputs continuous FIRE scores, dichotomous FIREs, and super-FIREs. Applying FIREcaller to Hi-C data from various human tissues, we demonstrate that FIREs and super-FIREs identified, in a tissue-specific manner, are closely related to gene regulation, are enriched for enhancer-promoter (E-P) interactions, tend to overlap with regions exhibiting epigenomic signatures of cis-regulatory roles, and aid the interpretation or GWAS variants. The FIREcaller package is implemented in R and freely available at https://yunliweb.its.unc.edu/FIREcaller.Highlights– Frequently Interacting Regions (FIREs) can be used to identify tissue and cell-type-specific cis-regulatory regions.– An R software, FIREcaller, has been developed to identify FIREs and clustered FIREs into super-FIREs.

scholarly journals Targeting Mycobacterial F-ATP Synthase C-Terminal α Subunit Interaction Motif on Rotary Subunit γ

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1456
Author(s):  
Amaravadhi Harikishore ◽  
Chui-Fann Wong ◽  
Priya Ragunathan ◽  
Dennis Litty ◽  
Volker Müller ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Atp Hydrolysis ◽  
Atp Synthesis ◽  
Membrane Vesicles ◽  
Α Subunit ◽  
Rotational States ◽  
C Terminus ◽  
Inverted Membrane Vesicles ◽  
Hydrolysis Of ◽  
Micromolar Range

Mycobacteria regulate their energy (ATP) levels to sustain their survival even in stringent living conditions. Recent studies have shown that mycobacteria not only slow down their respiratory rate but also block ATP hydrolysis of the F-ATP synthase (α3:β3:γ:δ:ε:a:b:b’:c9) to maintain ATP homeostasis in situations not amenable for growth. The mycobacteria-specific α C-terminus (α533-545) has unraveled to be the major regulative of latent ATP hydrolysis. Its deletion stimulates ATPase activity while reducing ATP synthesis. In one of the six rotational states of F-ATP synthase, α533-545 has been visualized to dock deep into subunit γ, thereby blocking rotation of γ within the engine. The functional role(s) of this C-terminus in the other rotational states are not clarified yet and are being still pursued in structural studies. Based on the interaction pattern of the docked α533-545 region with subunit γ, we attempted to study the druggability of the α533-545 motif. In this direction, our computational work has led to the development of an eight-featured α533-545 peptide pharmacophore, followed by database screening, molecular docking, and pose selection, resulting in eleven hit molecules. ATP synthesis inhibition assays using recombinant ATP synthase as well as mycobacterial inverted membrane vesicles show that one of the hits, AlMF1, inhibited the mycobacterial F-ATP synthase in a micromolar range. The successful targeting of the α533-545-γ interaction motif demonstrates the potential to develop inhibitors targeting the α site to interrupt rotary coupling with ATP synthesis.

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