A Novel Positive Regulatory Element That Enhances HamsterCYP2A8 Gene Expression Mediated by Xenobiotic Responsive Element

AGAMOUS-like 15 (AGL15) is a member of the MADS domain family of transcription factors (TFs) that can directly induce and repress target gene expression, and for which promotion of somatic embryogenesis (SE) is positively correlated with accumulation. An ethylene-responsive element binding factor-associated amphiphilic repression (EAR) motif of form LxLxL within the carboxyl-terminal domain of AGL15 was shown to be involved in repression of gene expression. Here, we examine whether AGL15′s ability to repress gene expression is needed to promote SE. While a form of AGL15 where the LxLxL is changed to AxAxA can still promote SE, another form with a strong transcriptional activator at the carboxy-terminal end, does not promote SE and, in fact, is detrimental to SE development. Select target genes were examined for response to the different forms of AGL15.

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Stress Modifies the Expression of Glucocorticoid-Responsive Genes by Acting at Epigenetic Levels in the Rat Prefrontal Cortex: Modulatory Activity of Lurasidone

International Journal of Molecular Sciences ◽

10.3390/ijms22126197 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6197

Author(s):

Paola Brivio ◽

Giulia Sbrini ◽

Letizia Tarantini ◽

Chiara Parravicini ◽

Piotr Gruca ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Chronic Stress ◽

Chronic Mild Stress ◽

Male Rats ◽

Mild Stress ◽

Experimental Conditions ◽

Glucocorticoid Responsive Element ◽

Responsive Element

Epigenetics is one of the mechanisms by which environmental factors can alter brain function and may contribute to central nervous system disorders. Alterations of DNA methylation and miRNA expression can induce long-lasting changes in neurobiological processes. Hence, we investigated the effect of chronic stress, by employing the chronic mild stress (CMS) and the chronic restraint stress protocol, in adult male rats, on the glucocorticoid receptor (GR) function. We focused on DNA methylation specifically in the proximity of the glucocorticoid responsive element (GRE) of the GR responsive genes Gadd45β, Sgk1, and Gilz and on selected miRNA targeting these genes. Moreover, we assessed the role of the antipsychotic lurasidone in modulating these alterations. Chronic stress downregulated Gadd45β and Gilz gene expression and lurasidone normalized the Gadd45β modification. At the epigenetic level, CMS induced hypermethylation of the GRE of Gadd45β gene, an effect prevented by lurasidone treatment. These stress-induced alterations were still present even after a period of rest from stress, indicating the enduring nature of such changes. However, the contribution of miRNA to the alterations in gene expression was moderate in our experimental conditions. Our results demonstrated that chronic stress mainly affects Gadd45β expression and methylation, effects that are prolonged over time, suggesting that stress leads to changes in DNA methylation that last also after the cessation of stress procedure, and that lurasidone is a modifier of such mechanisms.

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Intestinal Apolipoprotein A-IV Gene Transcription Is Controlled by Two Hormone-Responsive Elements: A Role for Hepatic Nuclear Factor-4 Isoforms

Molecular Endocrinology ◽

10.1210/me.2004-0462 ◽

2005 ◽

Vol 19 (9) ◽

pp. 2320-2334 ◽

Cited By ~ 22

Author(s):

Amena Archer ◽

Dominique Sauvaget ◽

Valérie Chauffeton ◽

Pierre-Etienne Bouchet ◽

Jean Chambaz ◽

...

Keyword(s):

Gene Expression ◽

Transgenic Mice ◽

Distal Region ◽

Proximal Region ◽

Dominant Negative ◽

Specific Expression ◽

Nuclear Factors ◽

Dominant Negative Form ◽

Responsive Element ◽

Hormone Responsive Element

Abstract In the small intestine, the expression of the apolipoprotein (apo) C-III and A-IV genes is restricted to the enterocytes of the villi. We have previously shown that, in transgenic mice, specific expression of the human apo C-III requires a hormone-responsive element (HRE) located in the distal region of the human apoA-IV promoter. This HRE binds the hepatic nuclear factors (HNF)-4α and γ. Here, intraduodenal injections in mice and infections of human enterocytic Caco-2/TC7 cells with an adenovirus expressing a dominant-negative form of HNF-4α repress the expression of the apoA-IV gene, demonstrating that HNF-4 controls the apoA-IV gene expression in enterocytes. We show that HNF-4α and γ functionally interact with a second HRE present in the proximal region of the human apoA-IV promoter. New sets of transgenic mice expressing mutated forms of the promoter, combined with the human apo C-III enhancer, demonstrate that, whereas a single HRE is sufficient to reproduce the physiological cephalo-caudal gradient of apoA-IV gene expression, both HREs are required for expression that is restricted to villi. The combination of multiple HREs may specifically recruit regulatory complexes associating HNF-4 and either coactivators in villi or corepressors in crypts.

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The Human Papillomavirus Type 31 Late 3′ Untranslated Region Contains a Complex Bipartite Negative Regulatory Element

Journal of Virology ◽

10.1128/jvi.76.12.5993-6003.2002 ◽

2002 ◽

Vol 76 (12) ◽

pp. 5993-6003 ◽

Cited By ~ 26

Author(s):

Sarah A. Cumming ◽

Claire E. Repellin ◽

Maria McPhillips ◽

Jonathan C. Radford ◽

J. Barklie Clements ◽

...

Keyword(s):

Gene Expression ◽

Human Papillomavirus ◽

High Risk ◽

Epithelial Cells ◽

Regulatory Element ◽

Capsid Proteins ◽

Cellular Proteins ◽

Late Gene Expression ◽

Hpv 16 ◽

Negative Regulatory Element

ABSTRACT The papillomavirus life cycle is tightly linked to epithelial cell differentiation. Production of virus capsid proteins is restricted to the most terminally differentiated keratinocytes in the upper layers of the epithelium. However, mRNAs encoding the capsid proteins can be detected in less-differentiated cells, suggesting that late gene expression is controlled posttranscriptionally. Short sequence elements (less than 80 nucleotides in length) that inhibit gene expression in undifferentiated epithelial cells have been identified in the late 3′ untranslated regions (UTRs) of several papillomaviruses, including the high-risk mucosal type human papillomavirus type 16 (HPV-16). Here we show that closely related high-risk mucosal type HPV-31 also contains elements that can act to repress gene expression in undifferentiated epithelial cells. However, the HPV-31 negative regulatory element is surprisingly complex, comprising a major inhibitory element of approximately 130 nucleotides upstream of the late polyadenylation site and a minor element of approximately 110 nucleotides mapping downstream. The first 60 nucleotides of the major element have 68% identity to the negative regulatory element of HPV-16, and these elements bind the same cellular proteins, CstF-64, U2AF65, and HuR. The minor inhibitory element binds some cellular proteins in common with the major inhibitory element, though it also binds certain proteins that do not bind the upstream element.

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