scholarly journals Spatial Learning Is Associated with Antagonist Outcomes for DNA Methylation and DNA Hydroxymethylation in the Transcriptional Regulation of the Ryanodine Receptor 3

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Rodrigo F. Torres ◽  
Bredford Kerr
Keyword(s):  
Dna Methylation ◽  
Transcriptional Regulation ◽  
Intracellular Calcium ◽  
Spatial Learning ◽  
Transcriptional Activity ◽  
Long Term Potentiation ◽  
Proximal Promoter ◽  
Calcium Stores ◽  
Dna Hydroxymethylation ◽  
Dna Modifications

Increasing attention has been drawn to the role that intracellular calcium stores play in neuronal function. Ryr3 is an intracellular calcium channel that contributes to hippocampal long-term potentiation, dendritic spine function, and higher cognitive processes. Interestingly, stimuli that increase neuronal activity upregulate the transcriptional activity of Ryr3 and augment DNA methylation in its proximal promoter. However, if these observations are valid for complex behavioral tasks such as learning and memory remains being evaluated. Relative expression analysis revealed that spatial learning increased the hippocampal levels of Ryr3, whereas mice trained using a visible platform that resulted in no spatial association showed reduced expression. Interestingly, we also observed that specific DNA modifications accompanied these opposite transcriptional changes. Increased DNA methylation was observed in hippocampal samples from spatially trained mice, and increased DNA hydroxymethylation was found in samples from mice trained using a visible platform. Both DNA modifications were not altered in control regions, suggesting that these changes are not generalized, but rather specific modifications associated with this calcium channel’s transcriptional regulation. Our two experimental groups underwent the same physical task differing only in the spatial learning component, highlighting the tight relationship between DNA modifications and transcriptional activity in a relevant context such as behavioral training. Our results complement previous observations and suggest that DNA modifications are a reliable signal for the transcriptional activity of Ryr3 and can be useful to understand how conditions such as aging and neuropathological diseases determine altered Ryr3 expression.

scholarly journals Transcriptional Regulation of PEN-2, a Key Component of the γ-Secretase Complex, by CREB

2006 ◽  
Vol 26 (4) ◽  
pp. 1347-1354 ◽  
Author(s):  
Ruishan Wang ◽  
Yun-wu Zhang ◽  
Ping Sun ◽  
Runzhong Liu ◽  
Xian Zhang ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Transcriptional Activity ◽  
Start Codon ◽  
Gamma Secretase ◽  
Mobility Shift ◽  
Endoproteolytic Cleavage ◽  
Notch Cleavage ◽  
Translational Start

ABSTRACT Gamma-secretase, which is responsible for the intramembranous cleavage of Alzheimer's β-amyloid precursor protein (APP), the signaling receptor Notch, and many other substrates, is a multiprotein complex consisting of at least four components: presenilin (PS), nicastrin, APH-1, and PEN-2. Despite the fact that PEN-2 is known to mediate endoproteolytic cleavage of full-length PS and APH-1 and nicastrin are required for maintaining the stability of the complex, the detailed physiological function of each component remain elusive. Unlike that of PS, the transcriptional regulation of PEN-2, APH-1, and nicastrin has not been investigated. Here, we characterized the upstream regions of the human PEN-2 gene and identified a 238-bp fragment located 353 bp upstream of the translational start codon as the key region necessary for the promoter activity. Further analysis revealed a CREB binding site located in the 238-bp region that is essential for the transcriptional activity of the PEN-2 promoter. Mutation of the CREB site abolished the transcriptional activity of the PEN-2 promoter. Electrophoretic mobility shift assays and chromatin immunoprecipitation analysis showed the binding of CREB to the PEN-2 promoter region both in vitro and in vivo. Activation of the CREB transcriptional factor by forskolin dramatically promoted the expression of PEN-2 mRNA and protein, whereas the other components of the γ-secretase complex remained unaffected. Forskolin treatment slightly increases the secretion of soluble APPα and Aβ without affecting Notch cleavage. These results demonstrate that expression of PEN-2 is regulated by CREB and suggest that the specific control of PEN-2 expression may imply additional physiological functions uniquely assigned to PEN-2.

Hippocampal long-term potentiation and spatial learning in the rat: effects of GABAB receptor blockade

Neuroscience ◽  
1996 ◽  
Vol 74 (2) ◽  
pp. 331-339 ◽  
Author(s):  
F.H Brucato ◽  
E.D Levin ◽  
D.D Mott ◽  
D.V Lewis ◽  
W.A Wilson ◽  
...  
Keyword(s):  
Spatial Learning ◽  
Gabab Receptor ◽  
Long Term Potentiation ◽  
Receptor Blockade ◽  
Term Potentiation

Dissociation between genes activated in long-term potentiation and in spatial learning in the rat

1998 ◽  
Vol 251 (1) ◽  
pp. 41-44 ◽  
Author(s):  
G Richter-Levin ◽  
K.L Thomas ◽  
S.P Hunt ◽  
T.V.P Bliss
Keyword(s):  
Spatial Learning ◽  
Long Term Potentiation ◽  
Term Potentiation

Retrovirus-induced interference with collagen I gene expression in Mov13 fibroblasts is maintained in the absence of DNA methylation

1991 ◽  
Vol 11 (1) ◽  
pp. 47-54
Author(s):  
H Chan ◽  
S Hartung ◽  
M Breindl
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chromatin Structure ◽  
Transcriptional Activity ◽  
Xenopus Laevis Oocytes ◽  
Regulatory Sequences ◽  
Type I ◽  
Wild Type ◽  
Col1a1 Gene

We have studied the role of DNA methylation in repression of the murine alpha 1 type I collagen (COL1A1) gene in Mov13 fibroblasts. In Mov13 mice, a retroviral provirus has inserted into the first intron of the COL1A1 gene and blocks its expression at the level of transcriptional initiation. We found that regulatory sequences in the COL1A1 promoter region that are involved in the tissue-specific regulation of the gene are unmethylated in collagen-expressing wild-type fibroblasts and methylated in Mov13 fibroblasts, confirming and extending earlier observations. To directly assess the role of DNA methylation in the repression of COL1A1 gene transcription, we treated Mov13 fibroblasts with the demethylating agent 5-azacytidine. This treatment resulted in a demethylation of the COL1A1 regulatory sequences but failed to activate transcription of the COL1A1 gene. Moreover, the 5-azacytidine treatment induced a transcription-competent chromatin structure in the retroviral sequences but not in the COL1A1 promoter. In DNA transfection and microinjection experiments, we found that the provirus interfered with transcriptional activity of the COL1A1 promoter in Mov13 fibroblasts but not in Xenopus laevis oocytes. In contrast, the wild-type COL1A1 promoter was transcriptionally active in Mov13 fibroblasts. These experiments showed that the COL1A1 promoter is potentially transcriptionally active in the presence of proviral sequences and that Mov13 fibroblasts contain the trans-acting factors required for efficient COL1A1 gene expression. Our results indicate that the provirus insertion in Mov13 can inactivate COL1A1 gene expression at several levels. It prevents the developmentally regulated establishment of a transcription-competent methylation pattern and chromatin structure of the COL1A1 domain and, in the absence of DNA methylation, appears to suppress the COL1A1 promoter in a cell-specific manner, presumably by assuming a dominant chromatin structure that may be incompatible with transcriptional activity of flanking cellular sequences.

scholarly journals Inositol 1,4,5 trisphosphate releases calcium from specialized sites within Limulus photoreceptors

1987 ◽  
Vol 104 (4) ◽  
pp. 933-937 ◽  
Author(s):  
R Payne ◽  
A Fein
Keyword(s):  
Endoplasmic Reticulum ◽  
Injection Site ◽  
Intracellular Calcium ◽  
Subcellular Distribution ◽  
Smooth Endoplasmic Reticulum ◽  
Image Intensifier ◽  
Photoreceptor Cells ◽  
Calcium Stores ◽  
Inositol 1,4,5 Trisphosphate ◽  
Probable Site

We have investigated the subcellular distribution and identity of inositol trisphosphate (InsP3)-sensitive calcium stores in living Limulus ventral photoreceptor cells, where light and InsP3 are known to raise intracellular calcium. We injected ventral photoreceptor cells with the photoprotein aequorin and viewed its luminescence with an image intensifier. InsP3 only elicited detectable aequorin luminescence when injected into the light-sensitive rhabdomeral (R)-lobe where aequorin luminescence induced by light was also confined. Calcium stores released by light and InsP3 are therefore localized to the R-lobe. Within the R-lobe, InsP3-induced aequorin luminescence was further confined around the injection site, due to rapid dilution and/or degradation of injected InsP3. Prominent cisternae of smooth endoplasmic reticulum are uniquely localized within the cell beneath the microvillar surface of the R-lobe (Calman, B., and S. Chamberlain, 1982, J. Gen. Physiol., 80:839-862). These cisternae are the probable site of InsP3 action.

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