p53 is an Important Regulator of CCL2 Gene Expression

Glucocorticoids are potent immunosuppressants which work in part by inhibiting cytokine gene transcription. We show here that NF-kappa B, an important regulator of numerous cytokine genes, is functionally inhibited by the synthetic glucocorticoid dexamethasone (DEX). In transfection experiments, DEX treatment in the presence of cotransfected glucocorticoid receptor (GR) inhibits NF-kappa B p65-mediated gene expression and p65 inhibits GR activation of a glucocorticoid response element. Evidence is presented for a direct interaction between GR and the NF-kappa B subunits p65 and p50. In addition, we demonstrate that the ability of p65, p50, and c-rel subunits to bind DNA is inhibited by DEX and GR. In HeLa cells, DEX activation of endogenous GR is sufficient to block tumor necrosis factor alpha or interleukin 1 activation of NF-kappa B at the levels of both DNA binding and transcriptional activation. DEX treatment of HeLa cells also results in a significant loss of nuclear p65 and a slight increase in cytoplasmic p65. These data reveal a second mechanism by which NF-kappa B activity may be regulated by DEX. We also report that RU486 treatment of wild-type GR and DEX treatment of a transactivation mutant of GR each can significantly inhibit p65 activity. In addition, we found that the zinc finger domain of GR is necessary for the inhibition of p65. This domain is also required for GR repression of AP-1. Surprisingly, while both AP-1 and NF-kappa B can be inhibited by activated GR, synergistic NF-kappa B/AP-1 activity is largely unaffected. These data suggest that NF-kappa B, AP-1, and GR interact in a complex regulatory network to modulate gene expression and that cross-coupling of NF-kappa B and GR plays an important role in glucocorticoid-mediated repression of cytokine transcription.

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Novel Regulation of CCL2 Gene Expression by Murine LITAF and STAT6B

PLoS ONE ◽

10.1371/journal.pone.0025083 ◽

2011 ◽

Vol 6 (9) ◽

pp. e25083 ◽

Cited By ~ 7

Author(s):

Xiaoren Tang ◽

Yu Yang ◽

Salomon Amar

Keyword(s):

Gene Expression ◽

Ccl2 Gene

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Upregulation of IL-6, IL-8 and CCL2 gene expression after acute inflammation: Correlation to clinical pain

Pain ◽

10.1016/j.pain.2009.02.001 ◽

2009 ◽

Vol 142 (3) ◽

pp. 275-283 ◽

Cited By ~ 69

Author(s):

Xiao-Min Wang ◽

May Hamza ◽

Tian-Xia Wu ◽

Raymond A. Dionne

Keyword(s):

Gene Expression ◽

Acute Inflammation ◽

Clinical Pain ◽

Ccl2 Gene

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Human Ribosomal RNA-Derived Resident MicroRNAs as the Transmitter of Information upon the Cytoplasmic Cancer Stress

BioMed Research International ◽

10.1155/2016/7562085 ◽

2016 ◽

Vol 2016 ◽

pp. 1-14 ◽

Cited By ~ 17

Author(s):

Masaru Yoshikawa ◽

Yoichi Robertus Fujii

Keyword(s):

Gene Expression ◽

Ribosomal Rna ◽

Ribosome Biogenesis ◽

Quantum Dynamic ◽

Rna Sequences ◽

Stem Loop ◽

Important Regulator ◽

Multiple Levels ◽

Cellular Stresses ◽

Nucleolar Rnas

Dysfunction of ribosome biogenesis induces divergent ribosome-related diseases including ribosomopathy and occasionally results in carcinogenesis. Although many defects in ribosome-related genes have been investigated, little is known about contribution of ribosomal RNA (rRNA) in ribosome-related disorders. Meanwhile, microRNA (miRNA), an important regulator of gene expression, is derived from both coding and noncoding region of the genome and is implicated in various diseases. Therefore, we performedin silicoanalyses using M-fold, TargetScan, GeneCoDia3, and so forth to investigate RNA relationships between rRNA and miRNA against cellular stresses. We have previously shown that miRNA synergism is significantly correlated with disease and the miRNA package is implicated in memory for diseases; therefore, quantum Dynamic Nexus Score (DNS) was also calculated using MESer program. As a result, seventeen RNA sequences identical with known miRNAs were detected in the human rRNA and termed as rRNA-hosted miRNA analogs (rmiRNAs). Eleven of them were predicted to form stem-loop structures as pre-miRNAs, and especially one stem-loop was completely identical withhsa-pre-miR-3678located in the non-rDNA region. Thus, these rmiRNAs showed significantly high DNS values, participation in regulation of cancer-related pathways, and interaction with nucleolar RNAs, suggesting that rmiRNAs may be stress-responsible resident miRNAs which transmit stress-tuning information in multiple levels.

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Tetrahymena thermophila JMJD3 Homolog Regulates H3K27 Methylation and Nuclear Differentiation

Eukaryotic Cell ◽

10.1128/ec.05290-11 ◽

2012 ◽

Vol 11 (5) ◽

pp. 601-614 ◽

Cited By ~ 16

Author(s):

Pei-Han Chung ◽

Meng-Chao Yao

Keyword(s):

Gene Expression ◽

Tetrahymena Thermophila ◽

Critical Role ◽

Content Type ◽

Chromatin Dynamics ◽

H3k27 Methylation ◽

Dna Elimination ◽

Severe Reduction ◽

Nuclear Development ◽

Important Regulator

ABSTRACT Histone H3K27me3 modification is an important regulator for development and gene expression. In Tetrahymena thermophila , the complex chromatin dynamics of H3K27me3 marks during nuclear development suggested that an H3K27me3 demethylase might exist. Here, we report an H3K27me3 demethylase homolog, JMJ1 , in Tetrahymena . During conjugation, JMJ1 expression is upregulated and the protein is localized first in the parental macronucleus and then in the new macronucleus. In conjugating cells, knockdown of JMJ1 expression resulted in a severe reduction in the production of progeny, suggesting that JMJ1 is essential for Tetrahymena conjugation. Furthermore, knockdown of JMJ1 resulted in increased H3K27 trimethylation in the new macronucleus and reduced transcription of genes related to DNA elimination, while the DNA elimination process was also partially blocked. Knockdown of the H3K27 methyltransferase EZL2 but not that of EZL1 partially restored progeny production in JMJ1 -knockdown cells and reduced abnormal H3K27me3 accumulation in the new macronucleus. Taken together, these results demonstrate a critical role for JMJ1 in regulating H3K27me3 during conjugation and the importance of JMJ1 in regulating gene expression in the new macronucleus but not in regulating the formation of heterochromatin associated with programmed DNA deletion.

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Short RNAs in environmental adaptation

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2006.3516 ◽

2006 ◽

Vol 273 (1594) ◽

pp. 1579-1585 ◽

Cited By ~ 9

Author(s):

Tamas Dalmay

Keyword(s):

Gene Expression ◽

Protein Complex ◽

Small Rnas ◽

Normal Development ◽

Environmental Adaptation ◽

Target Mrnas ◽

Short Rnas ◽

Recent Advances ◽

Perfect Complementarity ◽

Important Regulator

Non-coding small RNAs (19–24 nucleotide long) have recently been recognized as the important regulator of gene expression in both plants and animals. Several classes of endogenous short RNAs have partial or near perfect complementarity to mRNAs and a protein complex is guided by short RNAs to target mRNAs. The targeted mRNA is either cleaved or its translation is suppressed. Initially, short RNAs were believed to primarily regulate the normal development of plants and animals, but recent advances implicate short RNAs in environmental adaptation.

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Profiling of N6-methyladenosine dynamics indicates regulation of oyster development by m6A-RNA epitranscriptomes

10.1101/2021.08.30.458180 ◽

2021 ◽

Author(s):

Lorane Le Franc ◽

Bruno Petton ◽

Pascal Favrel ◽

Guillaume Riviere

Keyword(s):

Gene Expression ◽

Cell Differentiation ◽

Gene Expression Regulation ◽

Larval Stages ◽

Maternal To Zygotic Transition ◽

Morula Stage ◽

Important Regulator ◽

Global Increase ◽

And Shifts ◽

Developmental Significance

The N6-methylation of RNA adenosines (m6A) is an important regulator of gene expression with critical implications in vertebrate and insect development. However, the developmental significance of epitranscriptomes in lophotrochozoan organisms remains unknown. Using MeRIP-seq, we generated transcriptome-wide m6A-RNA methylomes covering the whole development of the oyster from oocytes to juveniles. Oyster RNA classes display specific m6A signatures, with mRNAs and lncRNAs exhibiting distinct profiles and being highly methylated compared to transposon transcripts. Epitranscriptomes are dynamic and correspond to chronological steps of development (cleavage, gastrulation, organogenesis and metamorphosis), with a minimal mRNA and lncRNA methylation at the morula stage followed by a global increase. mRNA m6A levels are correlated to transcript levels and shifts in methyladenine profiles correspond to expression kinetics. Differentially methylated transcripts cluster according to embryo-larval stages and bear the corresponding developmental functions (cell division, signal transduction, morphogenesis and cell differentiation). The m6A level of transposon transcripts is also regulated and peaks during the gastrulation. We demonstrate that m6A-RNA methylomes are dynamic and associated to gene expression regulation during oyster development. The putative epitranscriptome implication in the cleavage, maternal-to-zygotic transition and cell differentiation in a lophotrochozoan model brings new insights into the control and evolution of developmental processes.

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Differential gene expression reflects larval development and survival of monarch butterflies on different milkweed hosts

10.1101/2020.09.05.284489 ◽

2020 ◽

Author(s):

Pablo M. Gonzalez-De-la-Rosa ◽

Mariana Ramirez Loustalot-Laclette ◽

Cei Abreu-Goodger ◽

Therese Ann Markow

Keyword(s):

Gene Expression ◽

Environmental Factors ◽

Larval Development ◽

Larval Growth ◽

Danaus Plexippus ◽

Monarch Butterfly ◽

Hippo Signaling ◽

Asclepias Curassavica ◽

Important Regulator ◽

Differential Gene

ABSTRACTSecond instar larvae of the monarch butterfly, Danaus plexippus, from a nonmigratory population in Irapuato, Mexico, were reared for twenty-four hours on three species of milkweed hosts: Asclepias curassavica, A. linaria, and Gomphocarpus physocarpus. We then measured larval growth and differential expression of coding genes and of microRNAs. Larval growth was similar on the two Asclepias species, while little growth was observed on G. physocarpus. The greatest differences in coding gene expression occurred in genes controlling growth and detoxification and were most extreme in comparisons between G. physocarpus and the two Asclepias. MicroRNAs are predicted to be involved as regulators of many of these processes, in particular miR-278, differentially expressed here, could be an important regulator of growth through Hippo signaling. The implications for survival of the monarch, especially in the context of environmental factors altering the availability of their favored milkweed species, are discussed.

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C/EBPγ Suppresses Senescence and Inflammatory Gene Expression by Heterodimerizing with C/EBPβ

Molecular and Cellular Biology ◽

10.1128/mcb.01674-12 ◽

2013 ◽

Vol 33 (16) ◽

pp. 3242-3258 ◽

Cited By ~ 44

Author(s):

Christopher J. Huggins ◽

Radek Malik ◽

Sook Lee ◽

Jacqueline Salotti ◽

Sara Thomas ◽

...

Keyword(s):

Gene Expression ◽

Lung Tumor ◽

Gene Signature ◽

Dependent Manner ◽

Inflammatory Gene Expression ◽

Important Regulator ◽

Proinflammatory Gene ◽

Covalently Linked ◽

Nih 3T3 ◽

Oncogenic Stress

C/EBPβ is an important regulator of oncogene-induced senescence (OIS). Here, we show that C/EBPγ, a heterodimeric partner of C/EBPβ whose biological functions are not well understood, inhibits cellular senescence.Cebpg−/−mouse embryonic fibroblasts (MEFs) proliferated poorly, entered senescence prematurely, and expressed a proinflammatory gene signature, including elevated levels of senescence-associated secretory phenotype (SASP) genes whose induction by oncogenic stress requires C/EBPβ. The senescence-suppressing activity of C/EBPγ required its ability to heterodimerize with C/EBPβ. Covalently linked C/EBPβ homodimers (β∼β) inhibited the proliferation and tumorigenicity of RasV12-transformed NIH 3T3 cells, activated SASP gene expression, and recruited the CBP coactivator in a Ras-dependent manner, whereas γ∼β heterodimers lacked these capabilities and efficiently rescued proliferation ofCebpg−/−MEFs. C/EBPβ depletion partially restored growth of C/EBPγ-deficient cells, indicating that the increased levels of C/EBPβ homodimers inCebpg−/−MEFs inhibit proliferation. The proliferative functions of C/EBPγ are not restricted to fibroblasts, as hematopoietic progenitors fromCebpg−/−bone marrow also displayed impaired growth. Furthermore, highCEBPGexpression correlated with poorer clinical prognoses in several human cancers, and C/EBPγ depletion decreased proliferation and induced senescence in lung tumor cells. Our findings demonstrate that C/EBPγ neutralizes the cytostatic activity of C/EBPβ through heterodimerization, which prevents senescence and suppresses basal transcription of SASP genes.

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