In vivo DNase I-mediated footprinting analysis along the human bradykinin B1 receptor (BDKRB1) gene promoter: evidence for cell-specific regulation

By applying in vivo dimethyl sulphate and UV light type C-footprinting analysis, we previously showed that specific DNA sequences in the −1349/+42 core promoter region of the inducible human BDKRB1 (bradykinin B1 receptor) gene correlated with its transcriptional activity. In the present study we used the highly sensitive DNase I in vivo footprinting approach to delineate more precisely the functional domains of the BDKRB1 gene promoter in human SMCs (smooth muscle cells). Human lymphocytes that do not express a functional BDKRB1 were also studied as a reference using dimethyl sulphate, UV light type C and DNase I treatments. An obvious difference was found in the DNase I-footprinting patterns between cellular systems that express a functional BDKRB1 (SMCs) in comparison with human lymphocytes, where randomly distributed nucleosome-like footprinting patterns were found in the bulk of the core promoter region studied. Gel-shift assays and expression studies pointed to the implication of the YY1 and a TBP/TFIIB (TATA-box-binding protein/transcription factor IIB) transcription factor in the regulation of BDKRB1 gene expression in SMCs and possible YY1 involvement in the mechanisms of nuclear factor κB-mediated regulation of the receptor expression. No significant changes in the promoter foot-printing pattern were found after treatment with interleukin-1β or serum (known BDKRB1 gene inducers), indicating that definite regulatory motifs could exist outside the BDKRB1 gene core promoter region studied.

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Characterization of the rat intestinal Fc receptor (FcRn) promoter: transcriptional regulation of FcRn gene by the Sp family of transcription factors

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00131.2003 ◽

2004 ◽

Vol 286 (6) ◽

pp. G922-G931 ◽

Cited By ~ 12

Author(s):

Lingling Jiang ◽

Jiafang Wang ◽

R. Sergio Solorzano-Vargas ◽

Hugh V. Tsai ◽

Edgar M Gutierrez ◽

...

Keyword(s):

Transcriptional Regulation ◽

Cell Lines ◽

Promoter Region ◽

Core Promoter ◽

Dnase I ◽

Fc Receptor ◽

Minimal Promoter ◽

Luciferase Reporter ◽

Core Promoter Region

The regulatory elements that control the transcriptional regulation of the intestinal Fc receptor ( FcRn) have not been elucidated. The objective of this study was to characterize the core promoter region of the rat FcRn gene. Chimeric clones that contained various regions of the promoter located upstream of the luciferase reporter were transiently transfected into either IEC-6 or Caco-2 cell lines and nuclear extracts were used to perform DNase I footprint and DNA binding assays (EMSA). Transfection of chimeric upstream nested deletions-luciferase reporter clones into either of these cell lines supported robust reporter activity and identified the location of the minimal promoter at −157/+135. DNase I footprint analysis revealed two complexes located within the gene's core promoter region, and site-directed mutagenesis identified two regions that were critical to maintain basal expression. EMSA identified the presence of five Sp elements within the immediate promoter region that are capable of binding members of the Sp family of proteins. Among the five Sp elements, one element appears to not bind Sp1, Sp2, or Sp3 while influencing the interaction of Sp proteins with an adjacent Sp site. Overexpression of either Sp1 or Sp3 augments activity of the minimal promoter in Sp-deficient Drosophila SL2 cells. In summary, we report on the characterization of the rat FcRn minimal promoter, including the characterization of five Sp elements within this region that interact with members of the Sp family of transcriptional factors and drive promoter activity in intestinal cell lines.

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The −5 A/G single-nucleotide polymorphism in the core promoter region of MT2A and its effect on allele-specific gene expression and Cd, Zn and Cu levels in laryngeal cancer

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2014.08.016 ◽

2014 ◽

Vol 280 (2) ◽

pp. 256-263 ◽

Cited By ~ 7

Author(s):

Katarzyna Starska ◽

Anna Krześlak ◽

Ewa Forma ◽

Jurek Olszewski ◽

Alina Morawiec-Sztandera ◽

...

Keyword(s):

Gene Expression ◽

Single Nucleotide Polymorphism ◽

Promoter Region ◽

Core Promoter ◽

Specific Gene ◽

Nucleotide Polymorphism ◽

Core Promoter Region ◽

Single Nucleotide ◽

The Core ◽

Allele Specific

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The core promoter region of the tumor necrosis factor alpha gene confers phorbol ester responsiveness to upstream transcriptional activators.

Molecular and Cellular Biology ◽

10.1128/mcb.12.3.1352 ◽

1992 ◽

Vol 12 (3) ◽

pp. 1352-1356 ◽

Cited By ~ 29

Author(s):

D C Leitman ◽

E R Mackow ◽

T Williams ◽

J D Baxter ◽

B L West

Keyword(s):

Transcription Factors ◽

Tumor Necrosis Factor ◽

Promoter Region ◽

Tumor Necrosis ◽

Core Promoter ◽

Core Promoter Region ◽

Necrosis Factor Alpha ◽

The Core ◽

Factor Alpha ◽

Necrosis Factor

Activators of protein kinase C, such as 12-O-tetradecanoylphorbol 13-acetate (TPA), are known to regulate the expression of many genes, including the tumor necrosis factor alpha (TNF) gene, by affecting the level or activity of upstream transcription factors. To investigate the mechanism whereby TPA activates the TNF promoter, a series of 5'-deletion mutants of the human TNF promoter linked to chloramphenicol acetyltransferase was transfected into U937 human promonocytic cells. TPA produced a 7- to 11-fold activation of all TNF promoters tested, even those promoters truncated to contain only the core promoter with no upstream enhancer elements. The proximal TNF promoter containing only 28 nucleotides upstream and 10 nucleotides downstream of the RNA start site confers TPA activation to a variety of unrelated upstream enhancer elements and transcription factors, including Sp1, CTF/NF1, cyclic AMP-response element, GAL-E1a, and GAL-VP16. The level of activation by TPA depends on the TATA box structure, since the TPA response is greater in promoters containing the sequence TATAAA than in those containing TATTAA or TATTTA. These findings suggest that the core promoter region is a target for gene regulation by second-messenger pathways.

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The decapentaplegic core promoter region plays an integral role in the spatial control of transcription.

Molecular and Cellular Biology ◽

10.1128/mcb.15.7.3960 ◽

1995 ◽

Vol 15 (7) ◽

pp. 3960-3968 ◽

Cited By ~ 21

Author(s):

D H Schwyter ◽

J D Huang ◽

T Dubnicoff ◽

A J Courey

Keyword(s):

Expression Pattern ◽

Phase Ii ◽

Promoter Region ◽

Core Promoter ◽

Critical Role ◽

Regulatory Elements ◽

Drosophila Embryo ◽

Phase Iii ◽

Core Promoter Region ◽

Flanking Region

The Drosophila melanogaster decapentaplegic (dpp) gene encodes a transforming growth factor beta-related cell signaling molecule that plays a critical role in dorsal/ventral pattern formation. The dpp expression pattern in the Drosophila embryo is dynamic, consisting of three phases. Phase I, in which dpp is expressed in a broad dorsal domain, depends on elements in the dpp second intron that interact with the Dorsal transcription factor to repress transcription ventrally. In contrast, phases II and III, in which dpp is expressed first in broad longitudinal stripes (phase II) and subsequently in narrow longitudinal stripes (phase III), depend on multiple independent elements in the dpp 5'-flanking region. Several aspects of the normal dpp expression pattern appear to depend on the unique properties of the dpp core promoter. For example, this core promoter (extending from -22 to +6) is able to direct a phase II expression pattern in the absence of additional upstream or downstream regulatory elements. In addition, a ventral-specific enhancer in the dpp 5'-flanking region that binds the Dorsal factor activates the heterologous hsp70 core promoter but not the dpp core promoter. Thus, the dpp core promoter region may contribute to spatially regulated transcription both by interacting directly with spatially restricted activators and by modifying the activity of proteins bound to enhancer elements.

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High Frequency of Either Altered Pre-Core Start Codon or Weakened Kozak Sequence in the Core Promoter Region in Hepatitis B Virus A1 Strains from Rwanda

Genes ◽

10.3390/genes10030182 ◽

2019 ◽

Vol 10 (3) ◽

pp. 182 ◽

Cited By ~ 1

Author(s):

Heléne Norder ◽

Theogene Twagirumugabe ◽

Joanna Said ◽

Yarong Tian ◽

Ka-Wei Tang ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Promoter Region ◽

Core Promoter ◽

Etiologic Agent ◽

Start Codon ◽

Core Promoter Region ◽

Kozak Sequence ◽

The Core ◽

B Virus

Hepatitis B virus (HBV) is endemic in Rwanda and is a major etiologic agent for chronic liver disease in the country. In a previous analysis of HBV strains from Rwanda, the S genes of most strains segregated into one single clade of subgenotype, A1. More than half (55%) of the anti-HBe positive individuals were viremic. In this study, 23 complete HBV genomes and the core promoter region (CP) from 18 additional strains were sequenced. Phylogenetic analysis of complete genomes confirmed that most Rwandan strain formed a single unique clade, within subgenotype A1. Strains from 17 of 22 (77%) anti-HBe positive HBV carriers had either mutated the precore start codon (9 strains with either CUG, ACG, UUG, or AAG) or mutations in the Kozak sequence preceding the pre-core start codon (8 strains). These mutually exclusive mutations were also identified in subgenotypes A1 (70/266; 26%), A2 (12/255; 5%), and A3 (26/49; 53%) sequences from the GenBank. The results showed that previous, rarely described HBV variants, expressing little or no HBeAg, are selected in anti-HBe positive subgenotype Al carriers from Rwanda and that mutations reducing HBeAg synthesis might be unique for a particular HBV clade, not just for a specific genotype or subgenotype.

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