Transcriptional and posttranscriptional mechanisms regulate human renin gene expression in Calu-6 cells

1996 ◽  
Vol 271 (1) ◽  
pp. F94-F100 ◽  
Author(s):  
J. A. Lang ◽  
L. H. Ying ◽  
B. J. Morris ◽  
C. D. Sigmund
Keyword(s):  
Transcriptional Activity ◽  
De Novo ◽  
Gene Transfection ◽  
Fold Increase ◽  
Regulatory Elements ◽  
Human Renin ◽  
Renin Gene ◽  
A Cell ◽  
Silencer Element ◽  
Basal Transcriptional Activity

We have recently identified a human pulmonary carcinoma cell line (Calu-6) that expresses human renin (hREN) mRNA endogenously, and we use it herein as a model to examine the regulation of the hREN gene. Transfection analysis of a deletion series (-2750 to -149) of hREN promoter-luciferase fusion constructs revealed the presence of multiple weak regulatory elements within the first 1,301 bp of the 5'-flanking region and a classic silencer element within the first intron (intron A) of the gene. The 5'-flanking regulatory domain consisted of three closely linked elements, two negative and one positive, each contributing a cell-specific threefold modulation of transcriptional activity. Treating Calu-6 cells with forskolin caused a 100-fold increase in steady-state endogenous hREN mRNA but no increase in hREN promoter activity in transient transfections or in nuclear runoff transcription assays. Nevertheless, de novo transcription and translation were necessary for adenosine 3',5'-cyclic monophosphate (cAMP)-mediated induction. Our results suggest that multiple regulatory elements regulate basal transcriptional activity of the hREN gene and the increase in hREN mRNA by cAMP may be mediated by posttranscriptional mechanisms.

scholarly journals Identification of negative and positive regulatory elements in the human renin gene

1989 ◽  
Vol 264 (13) ◽  
pp. 7357-7362 ◽  
Author(s):  
D W Burt ◽  
N Nakamura ◽  
P Kelley ◽  
V J Dzau
Keyword(s):  
Regulatory Elements ◽  
Human Renin ◽  
Renin Gene

Regulatory elements of human renin gene expression

1987 ◽  
Vol 19 ◽  
pp. S48-S48 ◽  
Author(s):  
D BURT ◽  
P KELLEY ◽  
J FLYNN ◽  
A NAFTILAN ◽  
V DZAU
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Human Renin ◽  
Renin Gene

Characterization of a cell-specific human renin gene enhancer

1999 ◽  
Vol 17 (6) ◽  
pp. 858-858
Author(s):  
S Germain ◽  
F Bonnet ◽  
J Philippe ◽  
S Fuchs ◽  
P Corvol ◽  
...  
Keyword(s):  
Human Renin ◽  
Renin Gene ◽  
Gene Enhancer ◽  
A Cell

Effect of in vivo oestradiol treatment on cell-free transcription in trout liver nuclear extracts

1994 ◽  
Vol 13 (2) ◽  
pp. 137-147 ◽  
Author(s):  
F Delaunay ◽  
F Pakdel ◽  
Y Valotaire
Keyword(s):  
Dna Sequences ◽  
Transcriptional Activity ◽  
Hormonal Treatment ◽  
Fold Increase ◽  
Flanking Sequence ◽  
Transcription System ◽  
Nuclear Extracts ◽  
B1 Gene ◽  
A Cell

ABSTRACT In order to perform later studies on the transcriptional regulation of hormone-dependent genes in fish liver, we firstly examined the potential of trout liver nuclear extracts in a cell-free transcription system. As reporter genes, we used DNA sequences without G (G-free cassettes) under the control of three promoters derived from the 5′ flanking sequence of the Xenopus vitellogenin B1 gene; two of them were responsive to the oestrogen receptor (ER) through oestrogen responsive elements (ERE). Maximal transcriptional activity was obtained within a range of 40–130 μg protein per extract depending on the extract preparation. Transcription was maximal in reactions carried out at 25 °C. Similar transcriptional activities for the three promoters were observed when transcription was performed in extracts from untreated male trout. In contrast, we observed a 4·5- to 6-fold increase in the transcription with ERE-containing promoters in comparison with that with the minimal promoter bearing only a TATA box when extracts from oestradiol-treated male trout were used. This effect was correlated with the increase in the nuclear ER concentration induced by in vivo hormonal treatment. This enhanced transcription was specifically inhibited by the addition of a 25- to 100-fold excess of ERE oligonucleotide competitor. These data demonstrated, therefore, that transcription was ERE-dependent in this system and suggest strongly that it was mediated by the trout ER. Addition of oestradiol or the anti-oestrogens hydroxytamoxifen or ICI 164384 had no effect on the transcriptional activity of the two ERE-containing promoters, indicating that transcription was hormone-independent in trout liver nuclear extracts.

scholarly journals cis-regulatory elements and trans-acting factors directing basal and cAMP-stimulated human renin gene expression in chorionic cells.

1994 ◽  
Vol 74 (5) ◽  
pp. 764-773 ◽  
Author(s):  
P Borensztein ◽  
S Germain ◽  
S Fuchs ◽  
J Philippe ◽  
P Corvol ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Human Renin ◽  
Renin Gene

scholarly journals Sequence determinants of human gene regulatory elements

2021 ◽  
Author(s):  
Biswajyoti Sahu ◽  
Tuomo Hartonen ◽  
Paivi Pihlajamaa ◽  
Bei Wei ◽  
Kashyap Dave ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Transcriptional Activity ◽  
Cell Types ◽  
Regulatory Elements ◽  
Binding Motif ◽  
Atomic Unit ◽  
Gene Regulatory Elements ◽  
A Cell ◽  
Different Cell Types

DNA determines where and when genes are expressed, but the full set of sequence determinants that control gene expression is not known. To obtain a global and unbiased view of the relative importance of different sequence determinants in gene expression, we measured transcriptional activity of DNA sequences that are in aggregate ~100 times longer than the human genome in three different cell types. We show that enhancers can be classified to three main types: classical enhancers1, closed chromatin enhancers and chromatin-dependent enhancers, which act via different mechanisms and differ in motif content. Transcription factors (TFs) act generally in an additive manner with weak grammar, with classical enhancers increasing expression from promoters by a mechanism that does not involve specific TF-TF interactions. Few TFs are strongly active in a cell, with most activities similar between cell types. Chromatin-dependent enhancers are enriched in forkhead motifs, whereas classical enhancers contain motifs for TFs with strong transactivator domains such as ETS and bZIP; these motifs are also found at transcription start site (TSS)-proximal positions. However, some TFs, such as NRF1 only activate transcription when placed close to the TSS, and others such as YY1 display positional preference with respect to the TSS. TFs can thus be classified into four non-exclusive subtypes based on their transcriptional activity: chromatin opening, enhancing, promoting and TSS determining factors — consistent with the view that the binding motif is the only atomic unit of gene expression.

scholarly journals Interplay between Histone and DNA Methylation Seen through Comparative Methylomes in Rare Mendelian Disorders

2021 ◽  
Vol 22 (7) ◽  
pp. 3735
Author(s):  
Guillaume Velasco ◽  
Damien Ulveling ◽  
Sophie Rondeau ◽  
Pauline Marzin ◽  
Motoko Unoki ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Catalytic Domain ◽  
De Novo ◽  
Mutation Screening ◽  
Histone H3 ◽  
Regulatory Elements ◽  
Germline Mutations ◽  
Dna Methyltransferases ◽  
Mendelian Disorders ◽  
Epigenetic Machinery

DNA methylation (DNAme) profiling is used to establish specific biomarkers to improve the diagnosis of patients with inherited neurodevelopmental disorders and to guide mutation screening. In the specific case of mendelian disorders of the epigenetic machinery, it also provides the basis to infer mechanistic aspects with regard to DNAme determinants and interplay between histone and DNAme that apply to humans. Here, we present comparative methylomes from patients with mutations in the de novo DNA methyltransferases DNMT3A and DNMT3B, in their catalytic domain or their N-terminal parts involved in reading histone methylation, or in histone H3 lysine (K) methylases NSD1 or SETD2 (H3 K36) or KMT2D/MLL2 (H3 K4). We provide disease-specific DNAme signatures and document the distinct consequences of mutations in enzymes with very similar or intertwined functions, including at repeated sequences and imprinted loci. We found that KMT2D and SETD2 germline mutations have little impact on DNAme profiles. In contrast, the overlapping DNAme alterations downstream of NSD1 or DNMT3 mutations underlines functional links, more specifically between NSD1 and DNMT3B at heterochromatin regions or DNMT3A at regulatory elements. Together, these data indicate certain discrepancy with the mechanisms described in animal models or the existence of redundant or complementary functions unforeseen in humans.

scholarly journals Chromatin loop anchors contain core structural components of the gene expression machinery in maize

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Stéphane Deschamps ◽  
John A. Crow ◽  
Nadia Chaidir ◽  
Brooke Peterson-Burch ◽  
Sunil Kumar ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Resolution ◽  
Transcriptional Activity ◽  
Spatial Organization ◽  
Regulatory Elements ◽  
Open Chromatin ◽  
Maize Genome ◽  
Chromatin Loop ◽  
Structural Components ◽  
Chromatin Loops

Abstract Background Three-dimensional chromatin loop structures connect regulatory elements to their target genes in regions known as anchors. In complex plant genomes, such as maize, it has been proposed that loops span heterochromatic regions marked by higher repeat content, but little is known on their spatial organization and genome-wide occurrence in relation to transcriptional activity. Results Here, ultra-deep Hi-C sequencing of maize B73 leaf tissue was combined with gene expression and open chromatin sequencing for chromatin loop discovery and correlation with hierarchical topologically-associating domains (TADs) and transcriptional activity. A majority of all anchors are shared between multiple loops from previous public maize high-resolution interactome datasets, suggesting a highly dynamic environment, with a conserved set of anchors involved in multiple interaction networks. Chromatin loop interiors are marked by higher repeat contents than the anchors flanking them. A small fraction of high-resolution interaction anchors, fully embedded in larger chromatin loops, co-locate with active genes and putative protein-binding sites. Combinatorial analyses indicate that all anchors studied here co-locate with at least 81.5% of expressed genes and 74% of open chromatin regions. Approximately 38% of all Hi-C chromatin loops are fully embedded within hierarchical TAD-like domains, while the remaining ones share anchors with domain boundaries or with distinct domains. Those various loop types exhibit specific patterns of overlap for open chromatin regions and expressed genes, but no apparent pattern of gene expression. In addition, up to 63% of all unique variants derived from a prior public maize eQTL dataset overlap with Hi-C loop anchors. Anchor annotation suggests that < 7% of all loops detected here are potentially devoid of any genes or regulatory elements. The overall organization of chromatin loop anchors in the maize genome suggest a loop modeling system hypothesized to resemble phase separation of repeat-rich regions. Conclusions Sets of conserved chromatin loop anchors mapping to hierarchical domains contains core structural components of the gene expression machinery in maize. The data presented here will be a useful reference to further investigate their function in regard to the formation of transcriptional complexes and the regulation of transcriptional activity in the maize genome.

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